Inflammation Research[JOURNAL]
Sun
200 papers
The OX40-OX40L Co-stimulatory pathway in dermatology: emerging frontiers for therapeutic approaches.
Criado GJ, Bueno-Filho R, Zanetti MET … +2 more , Arruda LK, Criado PR
Inflamm Res · 2025 Nov · PMID 41266646 · Publisher ↗
The OX40/OX40L co-stimulatory signaling pathway plays a crucial role in T cell activation, differentiation, expansion, and survival across various human tissues, including the skin and mucosal surfaces. Alterations in th...
The OX40/OX40L co-stimulatory signaling pathway plays a crucial role in T cell activation, differentiation, expansion, and survival across various human tissues, including the skin and mucosal surfaces. Alterations in this pathway have been implicated in diverse immune-mediated skin conditions such as tumor microenvironments; atopic dermatitis, characterized by type 2 inflammation; psoriasis and hidradenitis suppurativa, associated with Th17 responses; vitiligo, involving dysregulated interferon-producing CD8 T cells. The complex interplay between mast cells expressing OX40L and T cells expressing OX40, which in some contexts can inhibit regulatory T cell (Treg) function and promote Th17 differentiation, underscores the therapeutic potential of either antagonizing or agonizing this co-stimulatory pathway. In this review, we discuss selected dermatological diseases in which the OX40/OX40L axis appears relevant to their immunopathogenesis and may serve as a potential therapeutic target.
LPCAT3-dependent remodeling of the phospholipids and lipid rafts is essential for vascular proinflammatory signaling and the development of atherosclerosis.
Kondreddy V, Magisetty J, Rawat P … +4 more , Kathirvel M, Jala RR, Devi BLAP, Singh SK
Inflamm Res · 2025 Nov · PMID 41236634 · Publisher ↗
BACKGROUND: Lysophosphatidyl choline acyltransferase 3 (LPCAT3) is crucially involved in the remodeling of phospholipids in the membranes through incorporation of arachidonic acid (ARA; 20:4). The ARA-derived eicosanoids...
BACKGROUND: Lysophosphatidyl choline acyltransferase 3 (LPCAT3) is crucially involved in the remodeling of phospholipids in the membranes through incorporation of arachidonic acid (ARA; 20:4). The ARA-derived eicosanoids aggravate leukocyte adhesion, inflammation, vascular dysfunction, thrombosis, and atherogenesis. This study found that LPCAT3 modulates lipid rafts and contributes to the raft assembly/organization essential for cytokine signaling. METHODS: RNAi-dependent silencing of LPCAT3 in the endothelial cells. EPA and DHA enrichment in the cells. Lipid raft isolation and analysis of proinflammatory signaling molecules. Diet-induced atherosclerosis in the mice. LPCAT3 siRNA lipid nanoparticles/ EPA, DHA therapy. RESULTS: RNAi-dependent silencing of LPCAT3 inhibits TNFα-induced translocation & ubiquitination of TNFR1-signaling complex into the lipid rafts. This is associated with the attenuated NF-κB activation, synthesis of cell-adhesion molecules, cytokines, leukocyte adhesion, vascular permeability and endothelial dysfunction. Intriguingly, LPCAT3 inhibition resulted in significantly greater accretion of EPA and DHA in the PC and PE at the expense of ARA, and potentially decreased the ARA-derived eicosanoids in the vascular endothelium. Therapeutic administration of LPCAT3 siRNA-lipid nanoparticles in the high fat fed- mice markedly lowered the plasma glucose, insulin, proinflammatory cytokines, eicosanoids, and attenuated the plaque formation in the aorta. Co-treatment of LPCAT3 siRNA-lipid nanoparticles with EPA/DHA significantly elevated the accretion of EPA/DHA levels in the heart tissues and nullified the plaque development in the mice. CONCLUSIONS: Our data revealed that LPCAT3-dependent remodeling of lipid rafts is essential for the TNF-induced signal transduction, NF-kB activation, and vascular inflammation. Administration of LPCAT3 siRNA-lipid nanoparticles and EPA/DHA is an effective strategy to combat atherosclerosis.
Regulation of macrophage transcriptional dynamics during acute and chronic wound repair.
Raja SR, Sk MH, Wajeed S … +8 more , Yangdol R, Yadav A, Jindal H, Fatima A, Siddiquie A, Pulakat L, Subramanian R, Baig MS
Inflamm Res · 2025 Nov · PMID 41236567 · Publisher ↗
Wound healing is a complex and tightly controlled physiological process that involves various cell types, among which macrophages play a critical role in tissue repair and regeneration. Transcription regulators influence...
Wound healing is a complex and tightly controlled physiological process that involves various cell types, among which macrophages play a critical role in tissue repair and regeneration. Transcription regulators influence gene expression in macrophages at several phases of wound healing, such as hemostasis, inflammation, proliferation, and remodeling. This article explores the transcription factors that regulate the activity of macrophages during wound healing and help in ECM remodeling. Understanding how these transcription regulators coordinate macrophage actions in response to cellular and molecular stimuli is essential for determining the process behind acute and chronic healing. This review highlights the therapeutic interventions through modulating transcriptional activity to improve wound healing and resolve fibrosis in chronic wounds. Furthermore, this review also explores the roles of transcription factors in macrophages, suggesting valuable insights into innovative strategies to improve tissue regeneration in chronic or pathological conditions.
Arthritogenicity of CD11b + Gr1 + myeloid cells is dependent on dual specificity phosphatase 6 (DUSP6).
Laragione T, Dos Santos BG, Harris C … +2 more , Goedeke L, Gulko PS
Inflamm Res · 2025 Nov · PMID 41217493 · Publisher ↗
OBJECTIVE: The dual specificity phosphatase 6 (DUSP6) was recently implicated in autoimmune arthritis pathogenesis. However, it remains unclear which cell mediates its pathogenic activity in a mouse model of rheumatoid a...
OBJECTIVE: The dual specificity phosphatase 6 (DUSP6) was recently implicated in autoimmune arthritis pathogenesis. However, it remains unclear which cell mediates its pathogenic activity in a mouse model of rheumatoid arthritis (RA). METHODS: Bone marrow (BM) CD11b + Gr1 + cells were isolated from DUSP6 +/+ mice and transferred into DUSP6 -/- recipients. Six weeks later mice were administered the KRN serum to induce arthritis (KSIA), and analyzed for arthritis severity clinical scores. The same strategy was used in the opposite direction with cells from DUSP6-/- cells transferred in DUSP6 +/+ mice. BM CD11b + Gr1 + cells from DUSP6 +/+ and DUSP6 -/ - were stimulated with PMA and used for RNA sequencing, and also used for real-time measurements of mitochondrial respiration with the Seahorse XF Analyzer. RESULTS: Transfer of CD11 + Gr1 + cells DUSP6 mice into DUSP6 mice reversed the arthritis protection observed in the knockout mice, and developed severe disease. Transfer of cells from DUSP6 into DUSP6 were not protective and mice still developed severe disease. Cells from DUSP6 +/+ mice had a significantly higher oxidative burst, and higher glycolysis, compared with reduced levels in DUSP6-/-. RNA sequencing analyses revealed an enrichment for differentially expressed genes implicated in RA, MAPK signaling, leukocyte differentiation and neutrophil degranulation, among others. CONCLUSION: We describe a new arthritogenic role for DUSP6, which is mediated by CD11b + Gr1 + cells and their glycolytic activity and oxidative burst. Our findings also implicate these myeloid cells in arthritis pathogenesis and raise the possibility that DUSP6 may be a good target for the development of new therapies for RA.
Post-translational modifications regulating microglial inflammation in central nervous system disorders: a review.
Wang X, Yang M, Wang Y … +1 more , Zhu F
Inflamm Res · 2025 Nov · PMID 41217460 · Publisher ↗
BACKGROUND: Microglia, the primary immune cells of the central nervous system, play a pivotal role in orchestrating neuroinflammatory responses and maintaining neural homeostasis. Post-translational modifications (PTMs)...
BACKGROUND: Microglia, the primary immune cells of the central nervous system, play a pivotal role in orchestrating neuroinflammatory responses and maintaining neural homeostasis. Post-translational modifications (PTMs) are critical regulators of microglial inflammatory activation, phagocytic capacity, and crosstalk with other neural cells. FINDINGS: This review highlights seven PTMs-phosphorylation, acetylation, methylation, ubiquitination, succinylation, SUMOylation, and lactylation-that are closely linked to the modulation of microglial inflammation. We discuss how these modifications shape microglial phenotypes during central nervous system diseases, particularly in the context of neuroinflammation, and explore their potential as therapeutic targets for inflammation-driven neuropathologies. IMPLICATIONS: Understanding the regulatory landscape of PTMs provides valuable insights into microglial biology and the mechanisms underlying neuroinflammatory disorders. This review aims to summarize current evidence and offer a concise overview that may assist future research on PTM-mediated regulation of microglial function and its relevance to neurological diseases.
Multiple circulating inflammatory proteins are associated with pathological lesions and kidney function decline in IgA nephropathy.
Kobayashi H, Murata Y, Akiya Y … +6 more , Matsuoka T, Otsuka H, Tsunemi A, Nakamura Y, Azuma M, Abe M
Inflamm Res · 2025 Nov · PMID 41196368 · Publisher ↗
INTRODUCTION: The clinical relevance of circulating inflammatory proteins in Immunoglobulin A nephropathy (IgAN) remains incompletely defined. We examined whether serum inflammatory proteins-particularly tumor necrosis f...
INTRODUCTION: The clinical relevance of circulating inflammatory proteins in Immunoglobulin A nephropathy (IgAN) remains incompletely defined. We examined whether serum inflammatory proteins-particularly tumor necrosis factor (TNF) receptor-related markers-track with disease severity and progression in IgAN. METHODS: We enrolled Japanese subjects undergoing native kidney biopsy with newly diagnosed IgAN (n = 134); disease controls with membranous nephropathy (n = 24), minimal change disease (n = 45), or lupus nephritis (n = 23); and healthy controls (n = 88). We measured 10 serum inflammatory proteins before renal biopsy and evaluated their levels in different glomerulonephritis. Additionally, we assessed associations between these proteins and clinical outcomes, including kidney function and histological changes in IgAN. RESULTS: Inflammatory proteins, especially TNF-R1, TNF-R2, TNF-R3, TNF-R7, and TNF-R27, were elevated in patients with IgAN and were associated with the severity of tubulointerstitial lesions. Among disease controls, membranous nephropathy and lupus nephritis also showed elevated TNF-receptor-related proteins, whereas minimal change disease did not. TNF-R7 showed a significant early increase, suggesting possible involvement in IgAN pathogenesis. Multivariable analysis indicated these proteins could predict kidney function decline. CONCLUSIONS: Specific circulating inflammatory proteins, particularly in the TNF receptor pathway, reflect disease activity and structural injury in IgAN and may help identify patients at higher risk of progression.
Navigating the complex landscape of DPP4 inhibition in inflammation: from novel mechanisms to unresolved translational challenges.
Yang D, Ye Z, Chen J … +2 more , Wang S, Wang G
Inflamm Res · 2025 Nov · PMID 41196367 · Publisher ↗
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RUNX1 promotes NSCLC progression by ACP5/SMAD3-mediated M2 macrophage polarization.
He C, Li Y, Gao N … +7 more , Fu B, Zhou F, Ni B, Bu J, Chen J, Kong X, Li P
Inflamm Res · 2025 Nov · PMID 41196341 · Publisher ↗
OBJECTIVE: Regarding the participation of RUNX1 in lung cancer, we investigated its mechanism in regulating M2 polarization of tumor-associated macrophages in lung cancer. METHODS: The extracted bone marrow cells were di...
OBJECTIVE: Regarding the participation of RUNX1 in lung cancer, we investigated its mechanism in regulating M2 polarization of tumor-associated macrophages in lung cancer. METHODS: The extracted bone marrow cells were differentiated into macrophages (BMDMs), followed by tumor-conditioned medium (CM) stimulation to simulate the impact of tumor cells on macrophages in vivo, and treatment with RUNX1 shRNA, or pCDNA3.1-ACP5 and SIS3. Macrophage polarization and cytokine secretion were assessed by flow cytometry and ELISA, followed by evaluations of RUNX1, ACP5, p-β-catenin, β-catenin and p-SMAD3 levels. The ACP5-β-catenin interaction was detected by Co-IP. BMDMs were co-cultured with Lewis lung carcinoma cells using Transwell. The malignant behaviors of cells were assessed by CCK-8 and Transwell assays. In vivo experiments were conducted to verify roles of RUNX1. RESULTS: Tumor-CM stimulated BMDM M2 polarization. RUNX1 was up-regulated in tumor-CM-stimulated macrophages and M2-type BMDMs, and was poorly expressed in M1-type BMDMs. RUNX1 knockdown induced M1 marker expression and reduced M2 marker expression, and repressed non-small cell lung cancer (NSCLC) cell malignant behaviors. The effects of RUNX1 silencing were partly abrogated by ACP5 overexpression. ACP5 interacted with β-catenin to promote SMAD3 phosphorylation. Downregulation of SMAD3 phosphorylation partially reversed tumor-CM-promoted BMDM M2 polarization and NSCLC cell malignant behaviors. RUNX1 promoted M2 polarization and NSCLC cell malignant behaviors by promoting ACP5-mediated SMAD3 phosphorylation. RUNX1 knockdown inhibited M2 polarization in LLC mice to suppress tumor growth in vivo. CONCLUSION: RUNX1 promoted BMDM M2 polarization by facilitating the interaction between ACP5 and β-catenin to elevate SMAD3 phosphorylation, thus promoting NSCLC progression.
PGC1α alleviates M1 macrophage polarization through dual regulation of succinate metabolism and TRAF5 expression to mitigate TLR4/NF-κB-driven inflammatory cascades and myocardial ischemia/reperfusion injury.
Leng J, Cao Z, Li L … +7 more , Hu D, Luo Y, Tu B, Cao X, Tao R, Jiang Y, Tie H
Inflamm Res · 2025 Nov · PMID 41196309 · Publisher ↗
OBJECTIVE: This study investigates the dual regulatory role of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α) in macrophage polarization and its therapeutic potential for mitigating myocardi...
OBJECTIVE: This study investigates the dual regulatory role of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α) in macrophage polarization and its therapeutic potential for mitigating myocardial ischemia/reperfusion injury (MI/RI). METHODS: By integrating in vivo murine myocardial MI/RI models with macrophage-specific genetic manipulation and multi-omics analyses, including transcriptomics, proteomics, and energy metabolomics, we comprehensively investigated the cardio-protective effects, immune regulation, and potential mechanism of PGC1α. Mechanistic validations were performed using macrophage hypoxia/reoxygenation models combined with gain- and loss-of-function experiments to elucidate the molecular interactions within the PGC1α-mediated signaling network. RESULTS: PGC1α emerged as a potential regulator of macrophage polarization through coordinated metabolic and protein regulation in MI/RI. It suppresses TLR4/NF-κB-driven inflammation via two prominent parallel pathways: (1) Metabolic control through SUCLG1/succinyl-CoA synthetase-mediated succinate generation; (2) negatively regulates protein by TRAF5 mRNA expression inhibition. This dual-axis regulation effectively dampens M1 macrophage polarization and pro-inflammatory cytokine storms. Furthermore, macrophage-specific PGC1α activation demonstrated cardio-protective effects by preserving cardiac function and reducing cardiomyocyte apoptosis. CONCLUSION: Our findings established PGC1α as a potential regulator of macrophage polarization in MI/RI, bridging mitochondrial energy metabolism and protein expression with immune responses. The PGC1α-SUCLG1/succinate axis and PGC1α-TRAF5 axis unveil therapeutic targets and potential mechanisms for modulating inflammation in MI/RI. Future studies should focus on translating these mechanisms into clinical interventions through pharmacological PGC1α activation.
Systemic sclerosis, main culprits and involved signaling pathways.
Sadatpour O, Azizan A, Kavosi H … +3 more , Vodjgani M, Farhadi E, Mahmoudi M
Inflamm Res · 2025 Nov · PMID 41196296 · Publisher ↗
Systemic sclerosis is an autoimmune connective tissue disease of unknown cause and diverse clinical manifestations. Vasospastic episodes (Raynaud's phenomenon), often triggered by cold or stress, typically appear at dise...
Systemic sclerosis is an autoimmune connective tissue disease of unknown cause and diverse clinical manifestations. Vasospastic episodes (Raynaud's phenomenon), often triggered by cold or stress, typically appear at disease onset. Cytokines, particularly TGF-β, act in the inflammatory and hypoxic microenvironment to drive fibrosis, which predominantly develops at inflammatory sites. Several cell types contribute to disease pathogenesis and fibrosis, including vascular endothelial cells, vascular smooth muscle cells, and fibroblasts in the extracellular matrix. Multiple signaling pathways are activated in these cells and promote disease progression. Endothelial and vascular smooth muscle cells respond to diverse ligands through pathways such as AKT, MAPK, and GPCR signaling, which promote fibrosis progression in the profibrotic and proinflammatory milieu. Cytokines are also important mediators of inflammation and fibrosis, particularly by acting on activated monocytes in the ECM and guiding them toward M1 or M2 macrophage polarization. In the early inflammatory stage, M1 macrophages predominate, while the fibrotic stage is characterized by increased M2 macrophage presence. ECM accumulation, resulting from TGF-β signaling in fibroblasts, provides integrins with ligands and promotes enhanced adhesion and migration of these cells. TGF-β, on the other hand, can transactivate the Ras pathway, promoting myofibroblast differentiation and enhancing pro-fibrotic effects.
A novel anti-acute lung injury mechanism of astilbin: inhibition of epithelial cells ferroptosis by targeting NRF2 activation via binding Val608 site of NRF2.
Fang C, Pang S, Chen K … +8 more , Wang G, Liu Q, Zhao B, Li B, Shi B, Guo Y, Cai J, Zhang Z
Inflamm Res · 2025 Oct · PMID 41165829 · Publisher ↗
OBJECTIVE AND DESIGN: Astilbin (ATB) is a newly discovered natural compound with anti-inflammatory and immunomodulatory effects. However, its effects and underlying mechanisms in acute lung injury (ALI) remain unclear. M...
OBJECTIVE AND DESIGN: Astilbin (ATB) is a newly discovered natural compound with anti-inflammatory and immunomodulatory effects. However, its effects and underlying mechanisms in acute lung injury (ALI) remain unclear. MATERIAL OR SUBJECTS: An ALI model was established by intratracheal injection of lipopolysaccharide (LPS) into the trachea of C57BL/6 mice. In vitro, MLE-12 cells were stimulated with LPS. ATB was administered as a pretreatment to C57BL/6 mice and MLE-12 cells. RESULTS: ATB significantly alleviated ALI and suppressed the inflammatory response induced by LPS. Further data suggested that ATB inhibited LPS-induced ferroptosis in epithelial cells by increasing GPX4 and xCT expression. Moreover, ATB promoted NRF2 nuclear translocation in the LPS-treated group, while NRF2 inhibition significantly reversed the protective effects of ATB on ferroptosis and inflammation. NRF2 knockout in vivo abolished the protective effects of ATB against ALI and epithelial cell ferroptosis. Mechanistically, ATB increased NRF2 activity by binding to the Val608 amino acid of NRF2. The effect of ATB in improving ALI and ferroptosis was significantly reduced in NRF2 Val608 mutant mice. CONCLUSION: ATB mitigated ALI by suppressing epithelial cell ferroptosis and activating the NRF2 pathway via binding to Val608 of NRF2.
Beyond CYP2C19: inflammation and angiogenesis gene variants drive clopidogrel resistance in CAD patients.
Hajer F, Malek A, Amani A … +6 more , Rahma O, Khaldoun BH, Abdelhak F, Asma O, Amel HK, Saoussen C
Inflamm Res · 2025 Oct · PMID 41165802 · Publisher ↗
BACKGROUND: Clopidogrel resistance remains a significant clinical challenge in coronary artery disease (CAD), with traditional explanations focusing on CYP450 polymorphisms. However, emerging evidence highlights the crit...
BACKGROUND: Clopidogrel resistance remains a significant clinical challenge in coronary artery disease (CAD), with traditional explanations focusing on CYP450 polymorphisms. However, emerging evidence highlights the critical role of inflammation and angiogenesis in modulating platelet reactivity and clopidogrel responsiveness. Genetic variants in these pathways may represent under recognized determinants of treatment failure. This pilot study investigated the association between single nucleotide polymorphisms (SNPs) in inflammation- (CCR2, CCL5, CCL2) and angiogenesis-related (KDR, VEGFA) genes and clopidogrel resistance. METHODS: In a cross-sectional study of 135 Tunisian CAD patients on dual antiplatelet therapy, clopidogrel response was assessed using VerifyNow P2Y12 assay (resistance defined as PRU ≥ 208). Nine SNPs were genotyped via PCR-RFLP. Associations were evaluated using logistic regression, adjusting for covariates. RESULTS: The CCL5 rs2280789-C allele conferred a 3.4-fold increased resistance risk (OR = 3.40 (1.54-7.48), p = 0.002), while the CCR2 rs1799864-A allele was protective (OR = 0.30 (0.10-0.84), p = 0.02). The KDR rs1870377-AA genotype tripled resistance odds (OR = 3.05 (1.05-8.83), p = 0.04). A polygenic model revealed synergistic effects: 53% of non-responders carried ≥ 2 risk genotypes (CCR2-GG, CCL5-TC, KDR-AA) vs. 15% of responders (OR = 6.51 (2.86-14.83), p < 0.001). No associations were found for VEGFA or CCL2 SNPs. CONCLUSION: Beyond CYP450-mediated metabolism, clopidogrel resistance is driven by immuno-vascular mechanisms involving CCL5-mediated thrombo-inflammation, CCR2-dependent monocyte recruitment, and VEGFR2-linked endothelial dysfunction. These findings advocate for precision antiplatelet strategies integrating inflammatory and angiogenic pathways to optimize therapy.
Antigen-specific reduced IgG inhibits cellular response in rat basophilic leukemia cells activated with multivalent antigen.
Iwase A, Suzuki R, Yokawa S … +1 more , Furuno T
Inflamm Res · 2025 Oct · PMID 41165797 · Publisher ↗
OBJECTIVE: The aim of this study was to investigate whether antigen-specific reduced IgG inhibits mast cell activation evoked by the aggregation of the high-affinity IgE receptor (FcεRI) in a manner similar to intact IgG...
OBJECTIVE: The aim of this study was to investigate whether antigen-specific reduced IgG inhibits mast cell activation evoked by the aggregation of the high-affinity IgE receptor (FcεRI) in a manner similar to intact IgG. MATERIALS: Rat basophilic leukemia (RBL-2H3) cells are used for a mast cell model. TREATMENT: Monovalent mouse anti-trinitrophenyl (TNP) IgG1 (75 kDa) was prepared by reducing the disulfide bond between the heavy chains using cysteamine hydrochloride. IgE-sensitized RBL-2H3 cells were stimulated with TNP-OVA, and reduced IgG1 was added 5 min after stimulation. METHODS: Degranulation and IL-4 secretion were measured 30 min and 3 h after TNP-OVA stimulation by β-hexosaminidase assay and ELISA, respectively. The intracellular distribution of SH2-containing inositol 5'-phosphatase 1 (SHIP1) was determined using immunostaining. Group differences were analyzed using the Tukey-Kramer test. RESULTS: Reduced IgG1 significantly inhibited degranulation and IL-4 secretion in antigen-stimulated RBL-2H3 cells to an extent similar to intact IgG1. Intracellular SHIP1 localized to the plasma membrane 5 min after the addition of reduced IgG1, mirroring the effect of intact IgG1. CONCLUSIONS: These results suggest that antigen-specific reduced IgG1 (monovalent) inhibits antigen-induced mast cell activation by activating SHIP1 through co-ligation of FcεRI and the low-affinity IgG receptor (FcγRIIB).
Aquaporins: a novel perspective in the treatment of lung diseases.
Wu M, Miao Z, Liu F … +10 more , Dai S, Li Y, Zhou T, Zhuo Q, Zhang H, Song Z, Nie H, Yong W, Zhang L, Liu Y
Inflamm Res · 2025 Oct · PMID 41144048 · Publisher ↗
BACKGROUND: Aquaporins (AQPs) are a class of channel proteins expressed on the cell membrane, responsible for facilitating the transport of water molecules and certain small solutes across the membrane. Their dysregulati...
BACKGROUND: Aquaporins (AQPs) are a class of channel proteins expressed on the cell membrane, responsible for facilitating the transport of water molecules and certain small solutes across the membrane. Their dysregulation is involved in the occurrence and progression of major lung diseases. FINDINGS: We systematically reviewed the expression and functional alterations of AQPs in acute lung injury (ALI), pneumonia, asthma, chronic obstructive pulmonary disease (COPD), pulmonary fibrosis (PF) and lung cancer, and integrated the potential molecular mechanisms. In addition, we examine the regulatory mechanisms of traditional Chinese medicine on lung AQPs, and summarizes the research progress of inhibitors and small molecular compounds that modulate AQPs in lung diseases. IMPLICATIONS: AQPs may serve as promising therapeutic targets for lung diseases. This review offers novel insights and a foundation for the diagnosis, treatment, and drug development of lung diseases, positioning AQPs as a potential tool in combating these conditions.
The SPI1/LILRB2 axis modulates macrophage tolerance via crosstalk with TLR8 signaling: implications for sepsis immunotherapy.
Yang D, Ye Z, Chen J … +3 more , Wang S, Yang J, Wang G
Inflamm Res · 2025 Oct · PMID 41144021 · Publisher ↗
The study by Bai and Guo (Biol Direct 20(1):73. https://doi.org/10.1186/s13062-025-00669-0 , 2025) offers significant insights into the molecular mechanisms of LPS tolerance in macrophages. The authors identify a novel p...
The study by Bai and Guo (Biol Direct 20(1):73. https://doi.org/10.1186/s13062-025-00669-0 , 2025) offers significant insights into the molecular mechanisms of LPS tolerance in macrophages. The authors identify a novel pathway wherein the transcription factor SPI1 (PU.1) directly upregulates the expression of the inhibitory receptor LILRB2, which in turn suppresses TLR8-mediated MyD88/NF-κB signaling to reinforce an immunosuppressive phenotype. While this work elegantly connects transcriptional regulation with functional immune modulation, several aspects warrant further discussion. The broad role of SPI1 necessitates confirming the specificity of its action on LILRB2 and excluding indirect effects on other tolerance regulators. The unconventional inhibition of TLR8, an endosomal viral RNA sensor, by LILRB2 raises questions about ligand specificity and context, particularly in scenarios of viral co-infection. Furthermore, the dominant role of TLR8 in LPS tolerance, a process canonically initiated by TLR4, merits additional validation to clarify its universality. Translational targeting of the SPI1/LILRB2 axis holds promise for reversing immune paralysis in sepsis or chronic inflammation, but potential risks demand careful evaluation using cell-specific approaches. Future work integrating epigenetic analyses, structural studies, single-cell transcriptomics from patients, and investigation of crosstalk with other immunoregulatory pathways will be crucial to fully establish the biological and clinical significance of these findings.
Oral citral attenuates alveolar bone loss and inflammation in ligature-induced periodontitis in rats.
Santos WS, Solon IG, Lopes PH … +2 more , Nascimento GC, Branco LGS
Inflamm Res · 2025 Oct · PMID 41144010 · Publisher ↗
BACKGROUND: In a ligature-induced periodontitis rat model, we tested oral citral (100 mg/kg, gavage) for 6 or 14 days and quantified alveolar bone loss, gingival cytokines, nitric oxide (NO), reactive oxygen species (ROS...
BACKGROUND: In a ligature-induced periodontitis rat model, we tested oral citral (100 mg/kg, gavage) for 6 or 14 days and quantified alveolar bone loss, gingival cytokines, nitric oxide (NO), reactive oxygen species (ROS), MMP-2 activity, and plasma TNF-α. METHODS: Adult male rats received a ligature around the first lower right molar for 7 or 15 days to induce periodontitis, while control animals remained unligated. Alveolar bone loss was assessed by measuring the cementoenamel junction-bone crest distance. Gingival cytokines (TNF-α, IL-1β, IL-6, IL-10) and plasma TNF-α were determined by ELISA, gingival NO by chemiluminescence, MMP-2 activity by gelatin zymography, and local ROS by in situ detection. RESULTS: Citral did not affect healthy gingiva. In ligature-induced periodontitis, a 14-day citral treatment significantly reduced alveolar bone loss, downregulated pro-inflammatory cytokines, increased IL-10, decreased plasma TNF-α levels, and inhibited both NO production and MMP-2 activity. ROS accumulation in the gingival tissue was also attenuated. CONCLUSION: These findings suggest that oral citral exhibits anti-inflammatory and antioxidant effects, thereby limiting alveolar bone loss in experimental periodontitis.
The connection between autophagy and Alzheimer's disease.
Lior N, Chen D, Dan F … +1 more , Ronit PK
Inflamm Res · 2025 Oct · PMID 41123674 · Full text
Alzheimer's disease (AD) is the most prevalent neurodegenerative disease associated with accumulation of amyloid beta peptides and intracellular neurofibrillary tangles formed by hyperphosphorylated Tau. Autophagy, an ev...
Alzheimer's disease (AD) is the most prevalent neurodegenerative disease associated with accumulation of amyloid beta peptides and intracellular neurofibrillary tangles formed by hyperphosphorylated Tau. Autophagy, an evolutionarily conserved process of self-degradation and turnover of cellular constituents, is important for normal cell growth but may be defective in diseases. A growing body of data implies that autophagy strongly affects AD pathogenesis. Autophagy mediates degradation of damaged organelles and proteins as well as neurotoxic aggregates, by regulating their clearance. Thus, impaired autophagy may account for the accumulation of protein aggregates. Since AD is characterized by neuroinflammation, impaired mitochondrial and lysosomal functions, and the accumulation of protein aggregates, the roles of autophagy/mitophagy in Alzheimer's will be extensively evaluated. In the current review, we will discuss the connection between autophagy/mitophagy and Alzheimer's. It seems that Alzheimer-related proteins such as APOE4, TREM2, PSEN1/2, APP and Tau can regulate autophagy. In turn, depending on the cellular system and animal model, autophagy regulating proteins such as Atg7, BECN1, GSK3B, MAP1LC3B, SQSTM1, TFEB and VCP can affect AD progression as discussed. We will also describe the effect of sex and lifestyle impact on autophagy and AD. Finally, we will describe how the current knowledge may contribute to potential therapeutic strategies.
Mitochondrial proteomics reveals the impact of Estrogen in enhancing energy metabolism of patient-derived fibroblast-like synoviocytes in rheumatoid arthritis.
Malik S, Chakraborty D, Agnihotri P … +5 more , Sarkar A, Joshi L, Saquib M, Kumar V, Biswas S
Inflamm Res · 2025 Oct · PMID 41123670 · Publisher ↗
Mitochondrial dysfunction drives Rheumatoid Arthritis (RA) progression by disturbing energy metabolism and promoting inflammation. Additionally, the female predominance of RA highlights estrogen deficiency as an importan...
Mitochondrial dysfunction drives Rheumatoid Arthritis (RA) progression by disturbing energy metabolism and promoting inflammation. Additionally, the female predominance of RA highlights estrogen deficiency as an important contributor to disease development. The effect of estrogen in RA has been investigated; however, its specific effects on the mitochondrial proteome and function have yet to be studied. This study investigated the effects of 17-β estradiol (E2) on the mitochondrial proteome of patient-derived RA fibroblast-like synoviocytes (RA-FLS) using Sequential Window Acquisition of all Theoretical Mass Spectra (SWATH-MS) analysis, followed by an assessment of key mitochondrial functional parameters and in vitro validation. The results identified an upregulated expression of two mitochondrial proteins, Acyl-CoA dehydrogenase very long chain (ACADVL) and ATP synthase subunit O (ATP5O), after E2 treatment in RA-FLS. This was further validated by increased real-time ATP production and reduced glycolytic capacity, along with increased expression of proteins related to fatty acid β-oxidation. In addition, E2 influenced mitochondrial dynamics by modulating the fission-fusion balance, resulting in improved mitochondrial morphology. E2 treatment also reduced the expression of mitophagy markers and increased mitochondrial membrane potential, indicating improved mitochondrial function. It also lowered mitochondria-centered oxidative stress by upregulating mitochondrial antioxidant enzymes. Mitochondrial proteomics analysis thus, demonstrated that E2 has the potential to enhance mitochondrial energy metabolism and alleviate mitochondrial dysfunction in RA. These findings provide a foundation for further exploration of mitochondria-targeted therapeutic approaches in RA management.
Long-pulsed 1064-nm neodymium: yttrium-aluminum-garnet laser alleviates rosacea by improving lymphatic vessel dysfunction.
Gu D, Pan R, Liu T … +9 more , Meng X, Ye Q, Hong C, Sun C, Wang Y, Yang W, Chen N, Liu W, Xu Y
Inflamm Res · 2025 Oct · PMID 41123652 · Publisher ↗
OBJECTIVE AND DESIGN: We aimed to investigate potential lymphatic vessel abnormalities associated with rosacea and elucidate effective rosacea treatment mechanism using long-pulsed 1064-nm neodymium: yttrium-aluminum-gar...
OBJECTIVE AND DESIGN: We aimed to investigate potential lymphatic vessel abnormalities associated with rosacea and elucidate effective rosacea treatment mechanism using long-pulsed 1064-nm neodymium: yttrium-aluminum-garnet laser (LPND). MATERIAL OR SUBJECTS: 32 female BALB/c mice were used to established the rosacea-like inflammation model and LPND treatment model. Human lymphatic endothelial cells (HLECs) were used for in vitro studies. TREATMENT: LL37 and/or LPND treatment. METHODS: Transcriptomic analyses and clinical observation were performed. Techniques such as Western blotting, immunofluorescence staining, flow cytometry, and clearance assays were employed to assess characteristics of lymphatic vessels. Statistical comparisons between two groups were conducted using Student's t-test or the Mann-Whitney U test, while comparisons among more than two groups were analyzed using one-way or two-way analysis of variance (ANOVA). RESULTS: Individuals with rosacea exhibited lymphatic dysfunction and LPND treatment could alleviate rosacea-associated clinical edema. Comparative analyses of acute and chronic mouse models revealed lymphatic vessel dilation, reduced density, and impaired function in chronic rosacea-like inflammation. LPND treatment mitigated chronic rosacea-like inflammation by ameliorating lymphatic vessel abnormalities. In vitro experiments demonstrated that LPND attenuated LL-37-induced inflammatory responses in HLECs. CONCLUSIONS: We elucidated the abnormalities of lymphatic vessels in rosacea and provided evidence supporting the targeted lymphatic vessel therapies.
Piezo1 exacerbates psoriasis by promoting macrophage M1 polarization and inhibits autophagy via activating PI3K/AKT signaling pathway.
Liu X, Du S, Jiang Y … +1 more , Chen Y
Inflamm Res · 2025 Oct · PMID 41123645 · Publisher ↗
OBJECTIVE AND DESIGN: This study was designed to delineate how Piezo1 orchestrates macrophage polarization and autophagy in psoriasis and to determine whether the PI3K/AKT axis mediates these effects. MATERIAL OR SUBJECT...
OBJECTIVE AND DESIGN: This study was designed to delineate how Piezo1 orchestrates macrophage polarization and autophagy in psoriasis and to determine whether the PI3K/AKT axis mediates these effects. MATERIAL OR SUBJECTS: Wild-type and Piezo1-knockout C57BL/6 mice were obtained from Vital River; human THP-1 monocytes and HaCaT keratinocytes were supplied by the Cell Bank of the Chinese Academy of Sciences. TREATMENT: Imiquimod was applied topically for six consecutive days; Piezo1 was silenced with shRNA, and autophagy was pharmacologically inhibited (10 mM 3-MA) or activated (200 nM rapamycin). METHODS: HE staining, immunohistochemistry and RNA-seq were performed in vivo. Western blot, immunofluorescence and flow cytometry quantified LC3-II/I, p62, PI3K/AKT proteins and CD86/CD206; cytokines were measured by ELISA. RESULTS: Piezo1 expression was significantly elevated in psoriatic lesions (P < 0.01). Genetic deletion of Piezo1 markedly attenuated disease severity, accompanied by an increased LC3-II/I ratio, reduced p62 accumulation, and a pronounced decline in inflammatory cytokine levels. Macrophages shifted from M1 to M2, suppressing keratinocyte proliferation and promoting apoptosis. RNA-seq confirmed the PI3K/AKT pathway as the key mediator. CONCLUSIONS: Piezo1 amplifies cutaneous inflammation by inhibiting autophagy and activating PI3K/AKT signalling to drive M1 macrophage polarization.
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