Journal Of Inflammation (London, England)[JOURNAL]
Sun
200 papers
Administration of human macrophage colony-stimulating factor-mFc fusion protein increases macrophage phagocytic capacity and stimulates liver regeneration in mice.
Starkey Lewis PJ, Cartwright JA, Campana L … +10 more , Baumgarten BU, Ebersbach H, Ludwig MG, Marszalek G, Stutchfield B, Aird R, Man TY, O'Duibhir E, Seuwen K, Forbes SJ
J Inflamm (Lond) · 2026 Jun · PMID 42351116 · Full text
BACKGROUND: Acute and chronic liver diseases are rising contributors of the worldwide healthcare burden. Inflammation plays a key role in progression of both acute and chronic disease, and effective treatments are limite...
BACKGROUND: Acute and chronic liver diseases are rising contributors of the worldwide healthcare burden. Inflammation plays a key role in progression of both acute and chronic disease, and effective treatments are limited. Macrophages, a diverse population of professional phagocytes, are required for the timely resolution of tissue injury and are an emerging target to treat acute and chronic liver disease. Colony stimulating factor 1 (CSF1), promotes differentiation and survival of macrophages, which are essential in epithelial regeneration, but the CSF1 protein is rapidly eliminated in vivo. We therefore fused human CSF1 genetically to a modified mouse IgG2a Fc region and transiently expressed this in HEK293-6E cells. The protein was purified from culture supernatant to obtain > 97% monomeric purity, suitable for in vivo testing. RESULTS: The nascent hCSF1-Fc fusion proteins were evaluated in vitro and in murine models of health and liver disease. hCSF1-mFc is pharmacologically active in healthy mice, resulting in increases in liver and spleen mass closely reflecting changes in tissue macrophage content. In an acetaminophen-induced acute liver injury model, hCSF1-mFc treatment increased hepatic macrophage accumulation at necrotic sites, reduced serum ALT activity, and serum IL-1β levels, and restored white blood cell counts within 72 h. Furthermore, hCSF1-mFc treatment also increased hepatic macrophage numbers in a carbon tetrachloride (CCl)-induced liver fibrosis model corresponding with a striking 3.5-fold increased uptake of a soluble phagocytic label, indicating improved hepatic clearance capacity. hCSF1-mFc was also tested in a model of acute on chronic liver injury, which included a bolus delivery of proinflammatory E. coli-coated bioparticles to pre-existing fibrosis. Here, hCSF1-mFc treatment restored body weight, induced hepatomegaly, and reduced several plasma pro-inflammatory cytokines, suggesting reduction of systemic inflammation. Finally, immunofluorescence staining showed hCSF1-mFc treatment induced significant hepatocyte proliferation in healthy and all liver disease models. CONCLUSION: This report demonstrates that hCSF1-mFc treatment increases liver macrophage populations, improves phagocytic capacity, and stimulates hepatocyte proliferation in experimental liver disease models. hCSF1-based fusion protein therapy might represent a novel immune-based strategy to treat acute and chronic liver disease in the clinic. CLINICAL TRIAL NUMBER: Not applicable.
Editorial Expression of Concern: The occurrence and development of radiation-induced lung injury after interstitial brachytherapy and stereotactic radiotherapy in SD rats.
Chen Z, Wang B, Wu Z … +6 more , Xiao H, Yang Y, Fan J, Gu Y, Chen C, Wu J
J Inflamm (Lond) · 2026 Jun · PMID 42260552 · Full text
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FOXD2-AS1/miR-185-5p/CDC42 axis in chronic obstructive pulmonary disease: clinical significance and mechanistic insights.
Xu J, Hu X, Wang Z … +5 more , Zhou Z, Chen T, Zhao X, Yang Y, Ding W
J Inflamm (Lond) · 2026 May · PMID 42141469 · Full text
BACKGROUND: Long non-coding RNA (lncRNA), a key molecule within gene expression regulatory network, is important in various respiratory diseases. This study assessed the expression changes and regulatory mechanism of lnc...
BACKGROUND: Long non-coding RNA (lncRNA), a key molecule within gene expression regulatory network, is important in various respiratory diseases. This study assessed the expression changes and regulatory mechanism of lncRNA FOXD2-AS1 in chronic obstructive pulmonary disease (COPD). MATERIALS AND METHODS: Two hundred COPD patients were enrolled, comprising 100 with AECOPD and 100 with stable COPD. 16HBE cells were exposed to cigarette smoke extract (CSE) to simulate disease conditions in vitro. Relative mRNA levels were measured via RT-qPCR. Cell function, including cell proliferation, apoptosis and inflammation, was assessed. Target binding genes were predicted using online tools, with their functions annotated via GO and KEGG analysis. RESULTS: Both stable COPD patients and AECOPD patients had significantly higher serum FOXD2-AS1 levels than healthy controls, with the highest values in AECOPD. It can differentiate stable COPD from healthy controls and AECOPD, and increased gradually with COPD stage progression. Silencing FOXD2-AS1 afforded protection against apoptotic and inflammatory phenotype induced by CSE in 16HBE cells. FOXD2-AS1 sponges miR-185-5p, which were downregulated in clinical serum samples and cell models. miR-185-5p downregulation reversed the effects of FOXD2-AS1 silencing on cell apoptosis and inflammation. CDC42, a downstream target of miR-185-5p, was upregulated in COPD patients and cell models, and negatively related to serum miR-185-5p levels. CDC42 reversed the role of FOXD2-AS1/ miR-185-5p in CSE-exposed 16HBE cells. CONCLUSIONS: Serum FOXD2-AS1 was markedly upregulated in COPD patients, with close correlation to disease severity. The FOXD2-AS1/miR-185-5p/CDC42 axis may contribute to COPD pathogenesis by mediating bronchial epithelial cell apoptosis and inflammation.
A spotlight on the inflammatory role of uremic toxins in the dysbiosis-CKD axis: a review.
Liaqat A
J Inflamm (Lond) · 2026 May · PMID 42116139 · Full text
There is growing evidence that gut-derived metabolites activate specific signaling pathways that lead to renal inflammation and injury, suggesting that the gut-kidney axis plays a significant role in the inflammatory pro...
There is growing evidence that gut-derived metabolites activate specific signaling pathways that lead to renal inflammation and injury, suggesting that the gut-kidney axis plays a significant role in the inflammatory processes that underlie chronic kidney disease (CKD). Alterations in the gut microbiota in CKD patients known as dysbiosis increases the production of uremic toxins such as p-cresyl sulfate, indoxyl sulfate and Trimethylamine N-oxide. These toxins trigger pro-inflammatory signaling pathways in renal tubular cells by initiating a series of inflammatory events, such as immune dysregulation, oxidative stress, and endotoxemia. As a result, cytokines like TNF-α, IL-6, and IL-1β are expressed more frequently, creating a chronic inflammatory environment that increase kidney damage and the progression of CKD. Emerging therapeutic strategies that alter gut microbiota composition, such as prebiotics, probiotics, dietary fiber, and fecal microbiota transplantation, have demonstrated promise in decreasing the burden of inflammation-inducing toxins. As research reveals new linkages between microbial metabolites and inflammatory signaling in CKD, addressing uremic toxin-mediated inflammation could revolutionize disease management. Understanding these interrelated signaling systems provides a more detailed understanding of how gut microbes influence renal inflammation at the molecular level. The aim of this review is to investigate the underlying signaling pathways by which gut-renal dysbiosis induces inflammation in CKD. The review attempts to guide the development of targeted treatment approaches that can reduce the inflammatory load and slow the progression of CKD by examining the mechanisms in which gut-derived uremic toxins alter oxidative stress, immunological responses, and inflammatory cascades.
Myeloperoxidase regulates hypoxia-induced inflammation and oxidative stress in liver-spleen axis.
Li Y, Liu X, Zhang L … +4 more , Li X, Zuo Z, Gao Q, Zhu Q
J Inflamm (Lond) · 2026 May · PMID 42069604 · Full text
BACKGROUND: High-altitude hypobaric hypoxia induces inflammation and oxidative stress, yet the role of myeloperoxidase (MPO) in this pathology remains incompletely understood. This study aimed to investigate whether MPO...
BACKGROUND: High-altitude hypobaric hypoxia induces inflammation and oxidative stress, yet the role of myeloperoxidase (MPO) in this pathology remains incompletely understood. This study aimed to investigate whether MPO mediates injury to the liverspleen axis under hypoxic conditions. RESULTS: Using a 3day murine hypoxia model, we unexpectedly found that MPO deficiency exacerbated, rather than mitigated, damage to the liverspleen axis. Compared with hypoxic wildtype mice, MPO mice displayed aggravated histopathological injury, accompanied by excessive phagocyte recruitment and elevated expression of key chemokines (KC, MCP1, MIP2) and proinflammatory mediators (TNFα, IL1β, IL17A). At the molecular level, MPO absence increased splenic protein expression of NFκB, NLRP3, and iNOS, while dysregulating the antioxidant response via the NRF2/HO1 pathway. CONCLUSIONS: These results reveal a novel protective role for MPO during hypoxic stress, where it functions to moderate the innate immune response and limit collateral tissue damage in the liverspleen axis. The study provides new insights into the complex immunomodulatory functions of MPO and suggests its activity is essential for maintaining immune homeostasis during acute hypoxia.
Resolvin D1 attenuates senescence-associated secretory phenotype independently of TGF-β-driven cardiac fibroblasts differentiation to myofibroblast.
Román M, Osorio JM, Espinoza-Pérez C … +5 more , Machuca V, Peiró C, Ferrer CS, Vivar R, Díaz-Araya G
J Inflamm (Lond) · 2026 Apr · PMID 42057012 · Full text
Cardiac fibroblasts (CF) are key regulators of myocardial inflammation through their ability to acquire senescent phenotypes and secrete inflammatory mediators. Although transforming growth factor-β (TGF-β) signaling is...
Cardiac fibroblasts (CF) are key regulators of myocardial inflammation through their ability to acquire senescent phenotypes and secrete inflammatory mediators. Although transforming growth factor-β (TGF-β) signaling is a central driver of myofibroblast differentiation, its contribution to inflammation-induced senescence and the senescence-associated secretory phenotype (SASP) remains poorly understood. In this study, we examined whether inflammatory stress induces senescence in adult rat CF independently of TGF-β signaling and evaluated the ability of Resolvin D1 (RvD1) to modulate the established SASP. Adult rat CF were treated with the ALK5 inhibitor SB431542 from isolation to prevent spontaneous myofibroblast differentiation. Cells were exposed to lipopolysaccharide (LPS, 1 μg/mL) under high (10%) serum conditions for 3 or 7 days. Senescence was assessed by cellular hypertrophy and SA-β-galactosidase activity. Following LPS stimulation, culture media were replaced and CF were treated with RvD1 for 48 h. Secreted cytokines, chemokines were quantified in conditioned media. LPS induced a robust senescent phenotype in CF, characterized by increased cell size and SA-β-galactosidase activity, regardless of TGF-β pathway inhibition or serum concentration. Inhibition of TGF-β signaling prevented myofibroblast differentiation but did not attenuate senescence induction. Importantly, RvD1 treatment significantly reshaped the SASP of senescent CF, reducing pro-inflammatory mediators including IL-1β, IL-6, TNF-α, and MCP-1, while preserving anti-inflammatory cytokines. These findings identify inflammatory stress as a driver of TGF-β–independent senescence in cardiac fibroblasts and highlight RvD1 as a potent modulator of senescence-associated inflammation.
Dihydromyricetin exerts neuroprotective effects in acute spinal cord injury by inhibiting NLRP3/Caspase-1 inflammasome through gut microbiome modeling.
Yang Y, Kang C, Pang R … +6 more , Huang S, He X, Gou X, Yang Y, Yan Y, Ma X
J Inflamm (Lond) · 2026 Apr · PMID 42001079 · Full text
BACKGROUND: The gut microbiota is closely associated with spinal cord injury (SCI). Dihydromyricetin (DHM), a potent anti-inflammatory compound with neuroprotective properties, has been shown to improve outcomes in vario...
BACKGROUND: The gut microbiota is closely associated with spinal cord injury (SCI). Dihydromyricetin (DHM), a potent anti-inflammatory compound with neuroprotective properties, has been shown to improve outcomes in various diseases. However, the role of gut microbiota mediating the mechanism neuroprotective effects of DHM in SCI is unknown. METHODS: Male Sprague-Dawley rats were randomly divided into three groups: SHAM, SCI, and DHM group. Motor function was assessed using the cylinder rearing test, and alterations in gut microbiota composition and metabolites were analyzed via 16S rRNA sequencing. Subsequently, Western blotting and immunofluorescence staining were employed to evaluate intestinal barrier integrity, as well as changes in proteins associated with the TLR4/NF-κB pathway and NLRP3/Caspase-1. Finally, fecal microbiota transplantation experiments were conducted to elucidate the necessity of gut microbiota in mediating the anti-inflammatory effects of DHM. RESULTS: DHM exhibits a therapeutic effect by attenuating the severity of pathological SCI and promoting motor function recovery. Notably, DHM restored a balanced microbiota pattern by increasing the relative abundance of Actinobacteria and Bacteroidetes, while concurrently decreasing that of Proteobacteria. Furthermore, DHM promoted intestinal barrier recovery, reduced blood lipopolysaccharide (LPS) levels, and suppressed the activation of the TLR4/NF-κB pathway and reduced the activity of the NLRP3/Caspase-1 inflammasome, thereby effectively decreasing the subsequent release of inflammatory factors in spinal cord tissue. Furthermore, the results from the two FMT groups demonstrated that the gut microbiota serves as a critical target for DHM to exert its anti-inflammatory effects. CONCLUSION: The results of this study demonstrate that restoring microbial balance, repairing intestinal barrier integrity, reducing serum LPS levels, and suppressing the TLR4/NF-κB pathway as well as NLRP3/Caspase-1 inflammasome activity constitute the key regulatory mechanisms underlying the neuroprotective effects of DHM following SCI, thereby opening up possibilities for a novel microbiome-directed therapeutic approach to SCI.
WWC1 deficiency exacerbates sepsis-induced lung injury by promoting NETosis, M1 and M2b macrophage recruitment, and pyroptosis via YAP1 and STING pathways.
Chen Y, Xu H, He C … +2 more , Qi Y, Chen Y
J Inflamm (Lond) · 2026 Apr · PMID 41998670 · Full text
BACKGROUND: Our recent investigations have shown that WWC1 loss leads to sepsis-induced lung injury (SiLI) by reducing activation of Yes-associated protein 1 (YAP1) and stimulator of interferon genes (STING) pathways. Th...
BACKGROUND: Our recent investigations have shown that WWC1 loss leads to sepsis-induced lung injury (SiLI) by reducing activation of Yes-associated protein 1 (YAP1) and stimulator of interferon genes (STING) pathways. This study further explores the involvements of pyroptosis, NETosis, and macrophage recruitment in the associated events. METHODS: Wild-type (wt) C57BL/6 mice, or mice with WWC1 gene knockout (WWC1-ko) or knock-in (WWC1-ki), were subjected to cecal ligation and puncture for SiLI modeling. Immunofluorescence staining and western blot (WB) were employed to analyze NETosis-related markers in lung tissues. Flow cytometry was employed to analyze the proportions of neutrophils and macrophages in bronchoalveolar lavage fluid (BALF). Immunohistochemistry and WB were applied to analyze pyroptosis markers. Histological staining was performed to analyze inflammatory responses in the lung tissues. Specific antagonists or agonists were utilized to analyze the involvements of YAP1 and STING in the inflammatory cascades. RESULTS: WWC1-ko mice showed more pronounced NETosis in the lung, accompanied by increased recruitment of neutrophils and macrophages, particularly M1 and M2b subtype macrophages, in the BALF. The pro-pyroptotic cascade was also activated in the lung of WWC1-ko mice. Administration of specific antagonists of NLRP3, YAP1, STING, and IRF3 reduced pyroptosis, alleviated NETosis, reduced abundance of macrophages, and mitigated inflammatory damage in the lung of WWC1-ko mice. By contrast, WWC1-ki mice were more resistant to these inflammatory cascades, which were, however, diminished upon the artificial activation of YAP1 or STING. CONCLUSION: The activation of pyroptosis, YAP1, and STING cascades upon WWC1 deficiency contributes to NETosis and accumulation of pro-inflammatory immune cells in SiLI.
Hypoxia synergizes cGAS-STING activation and AKT1 phosphorylation to drive pulmonary inflammation in one-lung ventilation: therapeutic attenuation by RU.521 and MK2206.
Zhang J, Zou Y, Chen D … +6 more , Fan J, Men B, Cai Y, Yuan X, Ye T, Cai K
J Inflamm (Lond) · 2026 Apr · PMID 41975472 · Full text
BACKGROUND: To explore the mechanisms involved in hypoxia-induced acute lung injury (ALI) and oxidative stress during one-lung ventilation (OLV) in order to find pharmacological interventions that can attenuate OLV injur...
BACKGROUND: To explore the mechanisms involved in hypoxia-induced acute lung injury (ALI) and oxidative stress during one-lung ventilation (OLV) in order to find pharmacological interventions that can attenuate OLV injury. METHODS: An OLV model was established in Sprague-Dawley (SD) rats. Lung tissue damage was assessed via histological staining and by quantifying inflammatory factors (TNF-α, IL-6, IL-1β) using qPCR. High-throughput transcriptome sequencing of left lung tissues from the OLV group and the two-lung ventilation (TLV) group screened for differentially expressed genes (DEGs) in pathways and biological functions associated with lung injury. Furthermore, a hypoxia reoxygenation (H/R) model was established using the mouse lung epithelial cell line (MLE-12) for further mechanism mapping and validation in vitro. RESULTS: Transcriptomic analysis revealed upregulated gene signatures linked to DNA damage, mitochondrial membrane permeabilization, oxidative stress, and innate immune activation. KEGG enrichment identified innate immune pathways, specifically cytosolic DNA sensing. Subsequent in vivo and in vitro studies confirmed cGAS-STING pathway activation, characterized by increased expression and enhanced phosphorylation of downstream components. Genetic knockdown of cGAS or AKT1 (a kinase required for downstream phosphorylation of key cGAS-STING downstream effectors) suppressed cGAS-STING pathway signaling. CONCLUSION: This study highlights that innate immunity contributes to lung tissue damage during OLV. Hypoxia-induced DNA damage activates the cytoplasmic DNA-sensing cGAS-STING pathway. Subsequently, AKT1 modulates the downstream phosphorylation of TBK1, IRF3, and NF-κB, thereby promoting DNA damage-associated inflammation in alveolar epithelial cells. Pharmacologically, both the cGAS inhibitor RU.521 and AKT1 inhibitor MK2206 attenuated cGAS-STING-mediated inflammation and mitigated hypoxia-induced oxidative stress in alveolar epithelia. CLINICAL TRIAL NUMBER: Not applicable.
Organ-specific inflammatory profiles during sepsis: divergent macrophage polarization and oxidative stress response in lung and liver in mouse model of caecal ligation and puncture.
Bodin A, Hammed A, Magnin M … +9 more , Bellaud P, Slek C, Commin L, Musso O, Corlu A, Lagente V, Aninat C, Louzier V, Victoni T
J Inflamm (Lond) · 2026 Apr · PMID 41963930 · Full text
BACKGROUND: Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection. Although systemic, sepsis mechanisms vary between organs. Macrophage activation or inhibition within specifi...
BACKGROUND: Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection. Although systemic, sepsis mechanisms vary between organs. Macrophage activation or inhibition within specific organs is thought to drive disease progression. Identifying organ-specific biomarkers could improve understanding of individual organ failure. This study compared the systemic inflammatory response in lung and liver, exploring macrophage involvement in compartmentalized responses using a murine polymicrobial sepsis model induced by cecal ligation and puncture (CLP). MATERIALS AND METHODS: Moderate sepsis was induced in male C57BL/6 mice divided into seven groups: Basal, Control (1 and 5 days), Sham (1 and 5 days), and CLP (1 and 5 days). Analyses included histology, lung and liver function (assessed via the ratio of arterial oxygen partial pressure to fractional inspired oxygen (PaO2/FiO2), bilirubin, and hepatic enzymes), and the measurement of cytokines and chemokines in blood, liver, and lung. We further analyzed oxidative stress markers—specifically Superoxide Dismutase (SOD) and Catalase (CAT) gens expression—macrophage activation states (using Cluster of Differentiation 86 (CD86) and 206 (CD206)), and Programmed Death-Ligand 1 (PD-L1) expression via immunohistochemistry. Tissue remodeling was assessed through Matrix Metalloproteinase (MMP) and Tissue Inhibitor of Metalloproteinase (TIMP) gene expression. RESULTS: Respiratory and liver dysfunction were evident at day 5 post-CLP by histology, decreased PaO2/FiO2, and increased bilirubin. Plasma TNF-α, IL-6, IL-10, and CCL2 peaked within 24 h and decreased by day 5, while cytokine profiles in organs differed from systemic levels. The lung showed elevated Ccl2, Ccr2, and Cx3cr1 expression compared to the liver, whereas the liver had a more pronounced oxidative imbalance. Lung tissue remodeling featured higher MMP expression with relatively lower inhibitors compared to the liver. Both organs showed increased CD86 and CD206 macrophage activation at day 5, but CD86-positive cells were three times more numerous in the liver, and CD206-positive cells were twice as high in the lung. Additionally, PD-L1 expression increased markedly in lung but not liver macrophages after CLP, affecting CD206⁺ subsets and suggesting lung-specific late immunosuppression. CONCLUSION: These findings support inflammatory compartmentalization in sepsis, with macrophages central to organ-specific immune regulation. Differential monocyte recruitment (CCL2/CCR2), oxidative stress, MMP/TIMP profiles and distinct CD86/CD206 distributions PD-L1 upregulation was restricted to CD206⁺ lung macrophages, reflecting late lung-specific immunosuppression. This emphasizes the potential of organ-targeted therapies and macrophage-related.
Electroacupuncture activates the TET1/PPARα pathway to protect mitochondrial function in MASLD.
Yang S, Li Y, Lu B … +3 more , Cheng C, Wang Y, Chen L
J Inflamm (Lond) · 2026 Apr · PMID 41928256 · Full text
BACKGROUND: Metabolic associated steatotic liver disease (MASLD), characterized by mitochondrial dysfunction. It may be ameliorated by electroacupuncture (EA) through activation of the ten-eleven translocation 1 (TET1)/p...
BACKGROUND: Metabolic associated steatotic liver disease (MASLD), characterized by mitochondrial dysfunction. It may be ameliorated by electroacupuncture (EA) through activation of the ten-eleven translocation 1 (TET1)/peroxisome proliferator-activated receptor-α (PPARα) pathway, thereby restoring mitochondrial function. METHODS: C57BL/6 mice were fed L-amino acid rodent diet with 60 kcal% fat, low methionine and no added choline (CDAHFD) and high fat diet (HFD) for three weeks to induce MASLD, followed by EA treatment and daily intraperitoneal injections of a TET1 agonist or antagonist. Hepatic lipid accumulation, inflammatory cytokines, reactive oxygen species (ROS), and mitochondrial function were evaluated by biochemical assays, enzyme-linked immunosorbent assay (ELISA), flow cytometry, and transmission electron microscopy (TEM), western blotting (WB) and reverse transcription quantitative polymerase chain reaction (RT-qPCR). RESULTS: EA reduced hepatic total cholesterol (TC), triglycerides (TG), and free fatty acids (FFA), and decreased the size of lipid droplets. It restored mitochondrial membrane potential, ATP production, and cristae integrity, while attenuating ROS accumulation and suppressing pro-inflammatory cytokine levels. Moreover, EA upregulated TET1 expression, enhanced genomic 5-hydroxymethylcytosine (5-hmC) enrichment, and elevated PPARα expression. These effects were comparable to those of a TET1 agonist, whereas administration of a TET1 antagonist partially reversed them. CONCLUSION: EA ameliorates MASLD by activating the TET1/PPARα pathway, thereby enhancing mitochondrial function and reducing oxidative stress and inflammation. CLINICAL TRIAL NUMBER: Not applicable.
Ubiquitination-mediated PRDX2 alleviates intervertebral disc degeneration via restraining TBHP-induced nucleus pulposus cell apoptosis, ferroptosis and ECM degradation.
Kong F, Luan J, Pan Q … +2 more , Qiao Y, Wang W
J Inflamm (Lond) · 2026 Mar · PMID 41877102 · Full text
BACKGROUND: Peroxiredogenase 2 (PRDX2) has been confirmed to be downregulated in patients with intervertebral disc degeneration (IDD). However, the role and mechanism of PRDX2 in the progression of IDD are still unclear....
BACKGROUND: Peroxiredogenase 2 (PRDX2) has been confirmed to be downregulated in patients with intervertebral disc degeneration (IDD). However, the role and mechanism of PRDX2 in the progression of IDD are still unclear. METHODS: Tert-butyl hydroperoxide (TBHP)-induced nucleus pulposus (NP) cells were used to construct IDD conditions. qRT-PCR or western blot was used to detect the expression levels of PRDX2, ubiquitin-specific protease 11 (USP11), ferroptosis-related markers and extracellular matrix (ECM)-related proteins. CCK8 assay, TUNEL assay and detection of ferroptosis-related markers were performed to examine cell viability, apoptosis and ferroptosis. Co-IP assay and ubiquitination assay were used to explore the regulation of USP11 on PRDX2. RESULTS: The expression levels of PRDX2 and USP11 were reduced in IDD patients and TBHP-induced NP cells. PRDX2 overexpression repressed TBHP-induced NP cell apoptosis, ferroptosis and ECM degradation. Moreover, our study found that USP11 stabilized the protein expression of PRDX2 by decreasing its ubiquitination. In addition, USP11 overexpression inhibited TBHP-induced NP cell apoptosis, ferroptosis and ECM degradation, while these effects were reversed by PRDX2 knockdown. CONCLUSION: USP11-mediated deubiquitination of PRDX2 might alleviate IDD progression by inhibiting TBHP-induced NP cell apoptosis, ferroptosis and ECM degradation, providing a potential intervention target worthy of further research for IDD.
Oral sodium butyrate supplementation acts on intestinal dysbiosis and resolves spinal cord neuroinflammation and nociceptive neuron sensitization.
Fusco A, Ricciardi F, Perrone M … +15 more , Di Martino E, Limongelli R, Morace AM, Finamore R, Bonsale R, Belardo C, Trotta MC, Iannotti FA, Infantino R, Luongo L, Schiraldi C, Di Marzo V, Maione S, Gatta A, Guida F
J Inflamm (Lond) · 2026 Mar · PMID 41862960 · Full text
BACKGROUND: Gut microbiota dysbiosis is a key pathological feature closely linked to metabolic disorders and neuroinflammation. It is typically characterized by reduced levels of beneficial microbial metabolites, particu...
BACKGROUND: Gut microbiota dysbiosis is a key pathological feature closely linked to metabolic disorders and neuroinflammation. It is typically characterized by reduced levels of beneficial microbial metabolites, particularly short-chain fatty acids (SCFAs) such as butyrate, and by increased production of pro-inflammatory molecules. In this study, we investigated the therapeutic potential of butyrate in a mouse model of antibiotic-induced gut dysbiosis, which is characterized by disruption of the normal gut microbiota and associated intestinal inflammation. RESULTS: We found that oral administration of sodium butyrate significantly reduced gut inflammation, as evidenced by decreased levels of the pro-inflammatory biomarkers calprotectin and lipocalin-2 in fecal samples compared with untreated dysbiotic mice. Furthermore, antibiotic treatment led to a marked reduction in specific butyrate-producing bacterial species, including Faecalibacterium prausnitzii and Roseburia spp. Notably, the abundance of these species, was partially restored following exogenous butyrate administration. Finally, butyrate administration significantly attenuated neuronal hyperexcitability in response to intracolonic distension and reduced pro-inflammatory factor levels in the spinal cord. CONCLUSIONS: These results highlight the role of butyrate in directly reducing gut inflammation and spinal neuroinflammation, while also promoting the restoration of some butyrate-producing bacteria. Our study underscores the potential of butyrate as a therapeutic agent for treating dysbiosis-associated gut inflammation and neuroinflammatory disorders, offering new insights into microbiota-targeted therapies for gut-brain axis regulation.
CRSwNP-derived cells retain native disease-relevant characteristics in vitro.
Kühnel P, Vossler L, Siemen M … +4 more , Sudhoff H, Todt I, Niehaus K, Schürmann M
J Inflamm (Lond) · 2026 Mar · PMID 41857733 · Full text
OBJECTIVE AND DESIGN: Chronic rhinosinusitis (CRS) is a heterogeneous inflammatory disease of the paranasal sinuses, which is divided into CRS with nasal polyps (CRSwNP) and CRS without nasal polyps (CRSsNP). CRSwNP is t...
OBJECTIVE AND DESIGN: Chronic rhinosinusitis (CRS) is a heterogeneous inflammatory disease of the paranasal sinuses, which is divided into CRS with nasal polyps (CRSwNP) and CRS without nasal polyps (CRSsNP). CRSwNP is typically caused by type 2 inflammation, which is characterized by elevated IL-4 and IL-13 levels, impairment of the epithelial barrier, and tissue remodeling. While the involvement of immune cells is well known, it remains unclear to what extent structural cells intrinsically maintain disease-specific functional programs. The aim of this study was to determine whether epithelial cells and fibroblasts derived from CRSwNP and CRSsNP differ in their barrier properties, inflammatory reactivity, and type 2-associated functional characteristics. METHODS: Air–liquid interface (ALI) epithelial cultures and primary fibroblast cultures were generated from CRSwNP and CRSsNP tissue. Epithelial barrier integrity was assessed by transepithelial electrical resistance (TEER), and inflammatory responses to TLR stimulation were analyzed by qRT-PCR. Fibroblast migration was evaluated using scratch assays. Cellular responses to IL-4/IL-13 with or without Dupilumab were quantified by qRT-PCR. RESULTS: CRSwNP-derived epithelial cells exhibited delayed tight junction formation and impaired differentiation compared to CRSsNP cells. Poly(I:C) stimulation induced stronger expression of Th2-associated cytokines in CRSwNP cultures. CRSwNP fibroblasts showed reduced migratory capacity and a heightened induction of Th2 cytokines and extracellular matrix genes following IL-4/IL-13 stimulation relative to CRSsNP fibroblasts. CONCLUSION: Epithelial cells and fibroblasts derived from CRSwNP retain disease-associated type 2 characteristics in vitro, indicating persistent disease-aligned programmed functional alterations of the polyp microenvironment. In contrast, CRSsNP-derived cells lacked comparable enhanced type 2 responsiveness. These findings support CRSwNP as a distinct, self-sustaining inflammatory endotype and underscore the value of patient-derived models for investigating disease mechanisms and targeted therapies.
The ErbB-tyrosine kinase inhibitor, neratinib, has anti-inflammatory effects in multimorbidity by increasing macrophage efferocytosis via the upregulation of MerTK.
Bowden KA, Wright C, Clark S … +5 more , Correa TF, Johnston SA, Marriott HM, Francis SE, Prince LR
J Inflamm (Lond) · 2026 Mar · PMID 41857730 · Full text
BACKGROUND: Chronic inflammatory disease is responsible for huge and increasing global mortality and morbidity. Unregulated inflammatory cells, including neutrophils and macrophages, are major drivers of chronic inflamma...
BACKGROUND: Chronic inflammatory disease is responsible for huge and increasing global mortality and morbidity. Unregulated inflammatory cells, including neutrophils and macrophages, are major drivers of chronic inflammatory disease. Efferocytosis plays a critical role in inflammation resolution by removing effete inflammatory cells from tissues. Despite defective efferocytosis being critical in inflammatory disease progression there are no therapies to correct these defects in clinical use. Here, using experimental models of atherosclerosis and lung injury, we identify the ErbB family tyrosine kinase inhibitor (TKI), neratinib, as a putative efferocytosis-targeting therapy. RESULTS: In an experimental model of atherosclerosis and lung injury, two doses of neratinib significantly increased efferocytosis in the lungs of mice concomitant with a reduction in the proportion of lung neutrophils. Neratinib significantly increased human neutrophil apoptosis and efferocytosis of apoptotic neutrophils by monocyte-derived macrophages (MDMs). In addition to increased efferocytosis, neratinib treated macrophages demonstrated both increased phagocytosis and macropinocytosis. Neratinib increased MDM surface expression of the efferocytosis receptor MerTK independent of protein synthesis and transcription which correlated with elevated efferocytosis in MDMs and inhibitors of MerTK blocked neratinib-induced efferocytosis. CONCLUSIONS: Thus, we describe a novel role for neratinib in driving efferocytosis in multimorbidity and suggest that ErbB TKIs may have therapeutic potential in inflammatory disease by restoring macrophage function and promoting inflammation resolution.
TCF4 contributes to OA progression by regulating the transcription of LOXL1.
Wang J, Liu X, Fan X … +2 more , Zhang Y, Ouyang H
J Inflamm (Lond) · 2026 Mar · PMID 41851702 · Full text
BACKGROUND: Osteoarthritis (OA) is a chronic degenerative joint disease that seriously affects patients’ quality of life. Lysyl oxidase like 1 (LOXL1), a member of the lysyl oxidase protein family, whose role in OA is un...
BACKGROUND: Osteoarthritis (OA) is a chronic degenerative joint disease that seriously affects patients’ quality of life. Lysyl oxidase like 1 (LOXL1), a member of the lysyl oxidase protein family, whose role in OA is unknown. METHODS: The gene expression pattern was investigated by the Gene Expression Omnibus database. Quantitative real-time PCR (qRT-PCR) and western blot were used to detect the gene expression in tissues and cells. Interleukin-1β (IL-1β) was applied to induce an inflammatory chondrocyte injury model in vitro, mimicking certain aspects of OA pathology, and the cell viability was measured by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl tetrazolium bromide (MTT) assay. 5-Ethynyl-2’-deoxyuridine (EdU) staining, flow cytometry, and enzyme linked immunosorbent assay (ELISA) assays were utilized for function examination. In addition, the monoiodoacetate (MIA)-induced arthritis mouse models were constructed to evaluate the effects of LOXL1 in vivo, and the hematoxylin-eosin (H&E) staining, safranin-O/fast green (SOFG) staining, and immunohistochemistry (IHC) were used to estimate the histological and morphological changes of the knee joints obtained from the mice. The transcriptional binding between genes was verified by chromatin immunoprecipitation (ChIP) and dual luciferase reporter assay. RESULTS: LOXL1 was up-regulated in tissues of OA. The down-regulation of LOXL1 promoted cell proliferation and inhibited apoptosis, inflammation, oxidative stress, and extracellular matrix (ECM) degradation in vitro. Meanwhile, LOXL1 knockdown exhibited the same results in vivo. Mechanically, transcription factor 4 (TCF4) activated the transcription of LOXL1, and TCF4 deficiency-mediated effects on chondrocyte injury were weakened by LOXL1. CONCLUSION: In summary, TCF4 may contribute to OA pathology by activating LOXL1 transcription, and the TCF4/LOXL1 axis is involved in IL-1β-induced chondrocyte dysfunction and MIA-induced joint degeneration.
Activated platelets promote endothelial dysfunction and monocyte recruitment in early renal microvascular injury.
Rustiasari UJ, Uil M, Zhang X … +7 more , Claessen N, Butter L, van Stalborch AD, Florquin S, van Buul JD, Tammaro A, Roelofs JJTH
J Inflamm (Lond) · 2026 Mar · PMID 41814324 · Full text
Chronic kidney disease (CKD) is characterized not only by progressive fibrosis but also by systemic endothelial dysfunction and inflammation. Platelets, traditionally recognized for their role in hemostasis, also serve a...
Chronic kidney disease (CKD) is characterized not only by progressive fibrosis but also by systemic endothelial dysfunction and inflammation. Platelets, traditionally recognized for their role in hemostasis, also serve as key modulators of endothelial activation and immune cell recruitment. Platelet activation is commonly observed in patients with CKD and contributes to the proinflammatory environment. Although platelet-endothelial interactions are well-characterized in cardiovascular disease, their role in renal endothelial dysfunction and inflammation remains poorly understood. To investigate this, we used the unilateral ureteral obstruction (UUO) model in mice, to examine how platelet activation influences endothelial responses and monocyte/macrophage recruitment in the early phase of renal fibrosis development. Platelet depletion reduced the number of infiltrating macrophages in kidney tissue, decreased expression of endothelial activation and inflammation markers, and preserved the peritubular capillary (PTC) integrity. Further in vitro studies using human umbilical vein endothelial cells (HUVECs) showed that activated platelets induced endothelial dysfunction and inflammation, in line with the in vivo findings. To recapitulate the vascular microenvironment, we performed a shear flow-based transmigration assay. Monocyte adhesion and transendothelial migration significantly increased when endothelial cells were pretreated with activated platelets compared to unstimulated controls. Moreover, the presence of platelets on the inflamed endothelium further enhanced monocyte migration, suggesting a synergistic effect in promoting immune cell recruitment. Collectively, our findings highlight that activated platelets contribute to endothelial dysfunction, inflammation, and monocyte infiltration in early kidney injury, suggesting their potential as a therapeutic target to mitigate microvascular injury and preserve renal vascular integrity in kidney disease.
Resolvin D1 alleviates liver inflammation and fibrosis through SIRT1-mediated NF-κB and TGF-β1/Smads pathways.
Li J, Zhao L, Xi Y … +1 more , Deng X
J Inflamm (Lond) · 2026 Mar · PMID 41776505 · Full text
OBJECTIVE: Resolvin D1 (RvD1) is lipid mediator converted from docosahexaenoic acid (DHA) and has multiple pharmacological properties. Recently, it has been reported that RvD1 alleviates tissue fibrosis, including renal...
OBJECTIVE: Resolvin D1 (RvD1) is lipid mediator converted from docosahexaenoic acid (DHA) and has multiple pharmacological properties. Recently, it has been reported that RvD1 alleviates tissue fibrosis, including renal and pulmonary fibrosis in animal models. Here, we investigate the effects of RvD1 on liver fibrosis models in vitro and in vivo and the underlying mechanism. METHODS: Male C57BL/6 mice treated with carbon tetrachloride (CCl4) and lipopolysaccharide (LPS)-activated LX-2 cells were used in the study. The serum levels of ALT and AST were analyzed to evaluate liver function. H&E and Sirius red staining were used to assess liver morphology and the degree of liver fibrosis. Quantitative RT-PCR and western blot were used to assay the gene expression and protein levels. RESULTS: In vivo, the results showed that RvD1 significantly attenuated increased AST and ALT serum levels in CCl4-treated mice. Histological examination revealed that RvD1 ameliorated CCl4-induced fibrous proliferation and macrophage infiltration. Besides, RvD1 depressed the expressions of pro-fibrotic factors (α-SMA, Collagen I and TIMP-1) and pro-inflammatory factors (IL-6, IL-1β, TNF-α and MCP-1) in the liver tissues of model mice. In vitro, RvD1 also relieved LPS-induced inflammation and hepatic stellate cell (HSC) activation in LX-2 cells. Furthermore, RvD1 was demonstrated to upregulate the expression of SIRT1, while inhibited the p-IκBα, p-NF-κB, TGF-β1, p-Smad2 and p-Smad3 protein levels in these models. CONCLUSIONS: Our results suggest that RvD1 alleviates liver inflammation and fibrosis through SIRT1-mediated NF-κB and TGF-β1/Smads pathways and may be used as a novel therapeutic intervention for liver fibrosis.
Quercetin-loaded silicon dioxide-graphene nanoparticles promotes M2 macrophage reprogramming in mycoplasma-induced pneumonia.
Liu X, Chen X, Jiang Y … +4 more , Li W, Fei X, Li X, Jiang Z
J Inflamm (Lond) · 2026 Feb · PMID 41715094 · Full text
OBJECTIVE: To develop and evaluate a quercetin-loaded silicon dioxide-graphene nanocomposite (Que@SiO₂-GNPs) for targeted macrophage modulation and epithelial protection in a Mycoplasma-induced pneumonia model. METHODS:...
OBJECTIVE: To develop and evaluate a quercetin-loaded silicon dioxide-graphene nanocomposite (Que@SiO₂-GNPs) for targeted macrophage modulation and epithelial protection in a Mycoplasma-induced pneumonia model. METHODS: Que@SiO₂-GNPs were synthesized via graphene oxide dispersion, sol-gel silica coating, and quercetin adsorption. Physicochemical properties were characterized by XPS, XRD, and FTIR. The therapeutic efficacy was evaluated in MP-infected rat models via histopathology, ELISA, flow cytometry, immunostaining, and Western blot. Cellular uptake, polarization, and functional assays were performed in primary AMs and BEAS-2B epithelial cells. RESULTS: Que@SiO₂-GNPs exhibited successful surface modification and quercetin incorporation with stable physicochemical properties. In vivo imaging demonstrated pulmonary targeting and favorable biocompatibility. In MP-infected rats, Que@SiO₂-GNPs significantly reduced pro-inflammatory cytokines (TNF-α, IL-6, IL-1β), alleviated lung injury, and promoted tissue repair. Mechanistically, the nanocomposites downregulated iNOS and CD86 while enhancing CD206 expression in AMs, indicating M2 polarization. Conditioned AMs improved epithelial proliferation, reduced oxidative stress and apoptosis, and upregulated SPLUNC1 expression. These outcomes were validated by EdU, ROS, Annexin V/PI, LDH assays, and protein expression analyses. CONCLUSIONS: Que@SiO₂-GNPs effectively reprogrammed macrophage phenotypes toward M2, suppressed inflammation, and conferred epithelial protection in Mycoplasma-induced pneumonia. This nanoplatform represents a promising immunomodulatory strategy for pulmonary infectious diseases. CLINICAL TRIAL NUMBER: Not applicable.
Simplified flow cytometric quantification of human neutrophil extracellular traps (NETs).
Rinaldi G, Cheng KKW, McCann C … +8 more , Rossi F, Rodriguez-Rios M, Dhaliwal K, Bebes A, Duncan L, Yuecel R, Rossi AG, Robb CT
J Inflamm (Lond) · 2026 Feb · PMID 41709215 · Full text
Several cellular pathways lead to the formation of neutrophil extracellular traps (NETs), a form of cell death (NETosis), distinct from apoptotic and necrotic cell death. Surprisingly, there remains a paucity of methods...
Several cellular pathways lead to the formation of neutrophil extracellular traps (NETs), a form of cell death (NETosis), distinct from apoptotic and necrotic cell death. Surprisingly, there remains a paucity of methods enabling efficient quantification of NETosis and associated pathways. Here, we describe the development of a simple, sensitive, reliable and flexible flow cytometry assay allowing efficient detection and quantification of NETosis. For the core assay, isolated primary human neutrophils were incubated with stimulants e.g. PMA/ionomycin with or without inhibitors prior to fixing. The fixed cells were then blocked and subsequently incubated in anti-DNA/Histone 1 and anti-histone H2A antibodies for dual detection of Histone 1 and Histone H2A. Cells with were H1-DNA/H2A double fluorescent were deemed NETotic. Imaging flow cytometry was used to validate the accuracy of NETosis detection/quantification. Several key pathways of NETosis were confirmed via the use of established NET-inducers in accordance with existing established methodologies. Importantly, our novel flow cytometry-based NETosis detection assay could efficiently discriminate NETosis from established neutrophil activation, as well as apoptotic and necrotic cell death. We believe our methodology will complement existing NETosis methodologies whilst concomitantly reducing human error, subjectivity and, indeed the false positivity (attained from neutrophil activation and other cell death processes) inherent in existing methodologies. Furthermore, the simplicity and flexibility of our methodology permit additional markers and pathways of NETosis to be investigated, highlighting it as an integral research tool for both general NETosis research and the pursuit to better understand the pathogenesis of NETosis-associated diseases.
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