Journal Of Inflammation (London, England)[JOURNAL]
Sun
200 papers
Effects of exogenous deoxyribonuclease I in collagen antibody-induced arthritis.
Macáková K, Borbélyová V, Tekeľová M … +7 more , Janko J, Pastorek M, Hokša R, Moravanský N, Šteňová E, Vlková B, Celec P
J Inflamm (Lond) · 2024 Sep · PMID 39251994 · Full text
BACKGROUND: Rheumatoid arthritis (RA) is associated with a high concentration of extracellular DNA (ecDNA). This could be a consequence of the inflammation, but the ecDNA could also be involved in the unknown etiopathoge...
BACKGROUND: Rheumatoid arthritis (RA) is associated with a high concentration of extracellular DNA (ecDNA). This could be a consequence of the inflammation, but the ecDNA could also be involved in the unknown etiopathogenesis of RA. Clearance of ecDNA is hypothesized to prevent the development of RA. This study aimed to analyze the effects of exogenous deoxyribonuclease I (DNase I) administration in an animal model of RA. METHODS: The collagen antibody-induced arthritis (CAIA) model of RA was induced in adult female DBA/1J mice. CAIA mice were treated with saline or DNase I (10 mg/kg) every 12 h for the whole duration of the experiment. Arthritic scores were assessed. Paw volume and temperature were assessed using a plethysmometer and a thermal camera, respectively. Plasma ecDNA and its subcellular origin were analyzed using fluorometry and real-time PCR. DNase activity was quantified with single radial enzyme diffusion method. RESULTS: The CAIA model was successfully induced as proved by a higher volume, temperature and the overall arthritis score in comparison to controls. The administration of DNase I resulted in a nearly two-fold increase in serum DNase activity. Still, it did affect neither plasma ecDNA, nor the arthritis score or other measures of joint inflammation. CONCLUSION: Our results suggest that exogenous DNase I does not prevent the development of CAIA in mice. Whether this is true for other animal models of arthritis or clinical RA requires further research. EcDNA does not seem to be involved in the pathogenesis of CAIA. Additional studies are also needed to elucidate the role of ecDNA in the development of RA, focusing especially on its origin and inhibition of ecDNA release.
Correction: PKM2/STAT1-mediated PD-L1 upregulation on neutrophils during sepsis promotes neutrophil organ accumulation by serving an anti-apoptotic role.
Li Y, Tan R, Li R … +6 more , Tian R, Liu Z, Wang X, Chen E, Pan T, Qu H
J Inflamm (Lond) · 2024 Sep · PMID 39232727 · Full text
Abstract loading — click title to view on PubMed.
Sonic Hedgehog reduces inflammatory response, decreases blood-spinal cord barrier permeability, and improves locomotor function recovery in an acute spinal cord injury rat model.
Tail M, Zhang H, Zheng G … +7 more , Harms AK, Hatami M, Skutella T, Kiening K, Unterberg A, Zweckberger K, Younsi A
J Inflamm (Lond) · 2024 Sep · PMID 39227870 · Full text
BACKGROUND: Sonic Hedgehog (Shh), extensively researched for its role in early neurogenesis and brain development, has recently been recognized for its neuroprotective potential following neuronal injuries. This study ex...
BACKGROUND: Sonic Hedgehog (Shh), extensively researched for its role in early neurogenesis and brain development, has recently been recognized for its neuroprotective potential following neuronal injuries. This study examines the immediate impact of early administered Shh on the local inflammatory response post-acute spinal cord injury in rats. METHODS: Thirty-four female Wistar rats underwent either sham surgery (laminectomy; n = 10) or clip compression/contusion spinal cord injury (SCI) at the T9 level. This was followed by implantation of an osmotic pump and a subdural catheter for continuous intrathecal delivery of Shh (n = 12) or placebo (NaCl; n = 12). Locomotor function was assessed at 3- and 7-days post-injury (dpi) using the Basso, Beattie, and Bresnahan (BBB) score and the Gridwalk test. Animals were euthanized after 3 or 7 days for immunohistochemical analysis of the local inflammatory reaction and immune cell migration. RESULTS: Shh-treated rats demonstrated significant hindlimb movement and coordination improvements at 7 days post-injury, compared to controls. This enhancement was accompanied by a significant reduction in both immune cell presence and blood plasma products within spinal cord lesions, suggesting Shh's dual role in modulating immune cell migration and maintaining the integrity of the blood-spinal cord barrier. Separately, these Shh-treated rats also showed an increase in M(IL-4) polarization of macrophages, further underlining the potential therapeutic impact of Shh in post-injury recovery. Notably, these effects were not evident at three days post-injury. CONCLUSION: Shh application at 7 days post-injury showed immunomodulatory effects, possibly via enhanced blood-spinal cord barrier integrity, reduced immune cell migration, and increased anti-inflammatory immune cell differentiation. These mechanisms collectively contribute to enhanced locomotor recovery.
The effects of chronic, continuous β-funaltrexamine pre-treatment on lipopolysaccharide-induced inflammation and behavioral deficits in C57BL/6J mice.
Hodge K, Buck DJ, Das S … +1 more , Davis RL
J Inflamm (Lond) · 2024 Sep · PMID 39223594 · Full text
BACKGROUND: Inflammation and neuroinflammation are integral to the progression and severity of many diseases and are strongly associated with cardiovascular disease, cancer, autoimmune disorders, neurodegenerative diseas...
BACKGROUND: Inflammation and neuroinflammation are integral to the progression and severity of many diseases and are strongly associated with cardiovascular disease, cancer, autoimmune disorders, neurodegenerative disease, and neuropsychiatric disorders. These diseases can be difficult to treat without addressing the underlying inflammation, and, as such, a growing need has arisen for pharmaceutical treatments that target inflammatory mediators and signaling pathways. Our lab has investigated the therapeutic potential of the irreversible µ-opioid antagonist β-funaltrexamine (β-FNA) and discovered that acute treatment ameliorates inflammation in astrocytes in vitro and inhibits central and peripheral inflammation and reduces anxiety- and sickness-like behavior in male C57BL/6J mice. Now, our investigation has expanded to investigate the chronic pre-treatment effects of β-FNA on lipopolysaccharide (LPS)-induced inflammation and behavior in male C57BL/6J mice. RESULTS: Micro-osmotic drug pumps were surgically inserted into the subcutaneous intrascapular space of male C57BL/6J mice. β-FNA or saline vehicle was continuously administered for seven days. On the sixth day, mice were given intraperitoneal injections of LPS or saline. An elevated plus maze test, followed by a forced swim test, were administered 24 h post-injection to measure sickness-, anxiety- and depressive-like behavior. Immediately after testing, frontal cortex, hippocampus, spleen, and plasma were collected. Levels of inflammatory chemokines C-C motif chemokine ligand 2 (CCL2) and C-X-C motif chemokine ligand 10 (CXCL10) were measured in tissues by enzyme-linked immunosorbent assay (ELISA). Quantitative reverse transcription polymerase chain reaction (RT-qPCR) was used to assess expression of the enzyme indoleamine 2, 3-dioxygenase 1 (IDO1) and the NLR family pyrin domain-containing protein 3 (NRLP3) inflammasome in frontal cortex and spleen tissues. Chronic pre-treatment robustly decreased inflammation in the hippocampus, frontal cortex, and spleen and reduced or abolished anxiety- and sickness-like behavior (e.g., increased time spent motionless, increased time spent in a contracted position, and reduced distance moved). However, treatment with β-FNA alone increased both inflammation in the frontal cortex and anxiety-like behavior. CONCLUSION: These findings provide novel insights into the anti-inflammatory and behavior-modifying effects of chronic β-FNA pre-treatment and continue to support the therapeutic potential of β-FNA under inflammatory conditions.
Mulberroside A mitigates intervertebral disc degeneration by inhibiting MAPK and modulating Ppar-γ/NF-κB pathways.
Xu T, Zhao H, Fang X … +5 more , Wang S, Li J, Wu H, Hu W, Lu R
J Inflamm (Lond) · 2024 Aug · PMID 39198816 · Full text
BACKGROUND: Intervertebral disc degeneration (IVDD) is a common spine disease with inflammation as its main pathogenesis. Mulberroside A (MA), isolated from herbal medicine, possesses anti-inflammatory characteristics in...
BACKGROUND: Intervertebral disc degeneration (IVDD) is a common spine disease with inflammation as its main pathogenesis. Mulberroside A (MA), isolated from herbal medicine, possesses anti-inflammatory characteristics in many diseases. Whereas, there is little exploration of the therapeutic potential of MA on IVDD. This study aimed at the therapeutic potential of MA on IVDD in vivo and in vitro and the mechanism involved. METHODS: In vitro, western blotting, RT-qPCR, and immunofluorescence analysis were implemented to explore the bioactivity of MA on interleukin-1 beta (IL-1β)-induced inflammation nucleus pulposus cells (NPCs) isolated from Sprague-Dawley male rats. In vivo, X-ray and MRI were applied to measure the morphological changes, and histological staining and immunohistochemistry were employed to investigate the histological changes of intervertebral disc sections on puncture-induced IVDD rat models. RESULTS: In vitro, MA up-regulated the expression level of anabolic-related proteins (Aggrecan and Collagen II) and decreased catabolic-related proteins (Mmp2, Mmp3, Mmp9, and Mmp13) in IL-1β-induced NPCs. Furthermore, MA inhibits the production of pro-inflammatory factors (Inos, Cox-2, and Il-6) stimulated by IL-1β. Mechanistically, MA inhibited the signal transduction of mitogen-activated protein kinase (MAPK) and nuclear factor kappa-B (NF-κB) pathways in IL-1β-induced NPCs. Moreover, MA might bind to Ppar-γ and then suppress the NF-kB pathway. In vivo experiment illustrated that MA mitigates the IVDD progression in puncture-induced IVDD model. X-ray and MRI images showed MA restore the disc height and T2-weighted signal intensity after puncturing. H&E and Safranin O/Fast Green also showed MA also alleviated morphological changes caused by acupuncture. In addition, MA reversed the expression level of Mmp13, Aggrecan, Collagen II, and Ppar-γ induced in IVDD models. CONCLUSIONS: MA inhibited degenerative phenotypes in NPCs and alleviated IVDD progression via inhibiting the MAPK and NF-κB pathways; besides, MA suppressed the NF-κB pathway was attributed to activating Ppar-γ, those supported that MA or Ppar-γ might be a potential drug or target for IVDD.
MicroRNA mediated suppression of airway lactoperoxidase by TGF-β1 and cigarette smoke promotes airway inflammation.
Santiago MJ, Chinnapaiyan S, Panda K … +6 more , Rahman MS, Ghorai S, Lucas JH, Black SM, Rahman I, Unwalla HJ
J Inflamm (Lond) · 2024 Aug · PMID 39192275 · Full text
Transforming Growth Factor Beta1 (TGF-β1) signaling is upregulated in Chronic Obstructive Pulmonary disease (COPD), smokers, and people living with HIV. Cigarette smoking and HIV are also independent risk factors for COP...
Transforming Growth Factor Beta1 (TGF-β1) signaling is upregulated in Chronic Obstructive Pulmonary disease (COPD), smokers, and people living with HIV. Cigarette smoking and HIV are also independent risk factors for COPD. Chronic inflammation is a hallmark of COPD. However, the underlying mechanisms remain unknown. Previous research has suggested that TGF-β1 alters the airway epithelial microRNAome and transcriptome, potentially contributing to lung inflammation. The Lactoperoxidase (LPO) system is an integral component of innate immunity within the airway. LPO plays a crucial role in host defense by catalyzing the oxidation of thiocyanate to hypothiocyanite in the presence of hydrogen peroxide (HO), generating a potent antibacterial and antiviral agent. Additionally, the LPO system potentially aids in maintaining cellular redox balance by reducing the levels of HO, thus mitigating oxidative stress within the airway epithelium. LPO dysfunction can impair immune responses and exacerbate inflammatory processes in respiratory diseases.In this study, primary bronchial epithelial cells and bronchial cell lines were treated with TGF-β1 and exposed to cigarette smoke to characterize the effect of these factors on LPO and their downstream effects. RT-qPCR and Western Blot were applied to quantify mRNA and proteins' expression. The levels of HO were detected using the Amplex Red Assay. Magnetofection and transfection were applied to probe the effect of miR-449b-5p. Staining procedures using the MitoTracker Green and C12FDG dyes were used to establish mitochondria mass and senescence. The levels of pro-inflammatory cytokines were measured via Luminex assays.We found that TGF-β1 and cigarette smoke suppressed airway LPO expression, increasing HO levels. This increase in HO had downstream effects on mitochondrial homeostasis, epithelial cellular senescence, and the pro-inflammatory cytokine response. We demonstrate for the first time that airway LPO is regulated by TGF-β1-induced miRNA-mediated post-transcriptional silencing through miR-449b-5p in the lungs. Further, we identify and validate miR-449-5p as the candidate miRNA upregulated by TGF-β1, which is involved in LPO suppression. This paper demonstrates a new mechanism by which TGF-β1 can lead to altered redox status in the airway.
Evidence of aberrant anti-epstein-barr virus antibody response, though no viral reactivation, in people with post-stroke fatigue.
Mouat IC, Zhu L, Aslan A … +5 more , McColl BW, Allan SM, Smith CJ, Buckwalter MS, McCulloch L
J Inflamm (Lond) · 2024 Aug · PMID 39135051 · Full text
BACKGROUND: Fatigue is a common complication of stroke that has a significant impact on quality of life. The biological mechanisms that underly post-stroke fatigue are currently unclear, however, reactivation of latent v...
BACKGROUND: Fatigue is a common complication of stroke that has a significant impact on quality of life. The biological mechanisms that underly post-stroke fatigue are currently unclear, however, reactivation of latent viruses and their impact on systemic immune function have been increasingly reported in other conditions where fatigue is a predominant symptom. Epstein-Barr virus (EBV) in particular has been associated with fatigue, including in long-COVID and myalgic encephalomyelitis/chronic fatigue syndrome, but has not yet been explored within the context of stroke. AIMS: We performed an exploratory analysis to determine if there is evidence of a relationship between EBV reactivation and post-stroke fatigue. METHODS: In a chronic ischemic stroke cohort (> 5 months post-stroke), we assayed circulating EBV by qPCR and measured the titres of anti-EBV antibodies by ELISA in patients with high fatigue (FACIT-F < 40) and low fatigue (FACIT-F > 41). Statistical analysis between two-groups were performed by t-test when normally distributed according to the Shapiro-Wilk test, by Mann-Whitney test when the data was not normally distributed, and by Fisher's exact test for categorical data. RESULTS: We observed a similar incidence of viral reactivation between people with low versus high levels of post-stroke fatigue (5 of 22 participants (24%) versus 6 of 22 participants (27%)). Although the amount of circulating EBV was similar, we observed an altered circulating anti-EBV antibody profile in participants with high fatigue, with reduced IgM against the Viral Capsid Antigen (2.244 ± 0.926 vs. 3.334 ± 2.68; P = 0.031). Total IgM levels were not different between groups indicating this effect was specific to anti-EBV antibodies (3.23 × 10 ± 4.44 × 10 high fatigue versus 4.60 × 10 ± 9.28 × 10 low fatigue; P = 0.288). CONCLUSIONS: These data indicate that EBV is not more prone to reactivation during chronic stroke recovery in those with post-stroke fatigue. However, the dysregulated antibody response to EBV may be suggestive of viral reactivation at an earlier stage after stroke.
Impairment of Nrf2 signaling in the hippocampus of P301S tauopathy mice model aligns with the cognitive impairment and the associated neuroinflammation.
Mohamed AS, ElKaffas M, Metwally K … +8 more , Abdelfattah M, Elsery EA, Elshazly A, Gomaa HE, Alsayed A, El-Desouky S, El-Gamal R, Elfarrash S
J Inflamm (Lond) · 2024 Aug · PMID 39107774 · Full text
Mice transgenic for human P301S tau protein exhibit many characteristics of the human tauopathies, including the formation of abundant hyperphoshorylated tau filaments, the associated neuroinflammation and disease phenot...
Mice transgenic for human P301S tau protein exhibit many characteristics of the human tauopathies, including the formation of abundant hyperphoshorylated tau filaments, the associated neuroinflammation and disease phenotype. However, the exact underpinning mechanisms are still not fully addressed that hinder our understanding of the tauopathy diseases and the development of possible therapeutic targets.Methods: In the current study, hippocampus from three disease time points (2, 4 and 6 months) of P301S mice were further characterized in comparison to the age and sex matched control wild type mice (WT) that do not express the transgene. Different spectrum of hippocampal dependent cognitive tests, biochemical and pathological analysis were conducted to understand the disease progression and the associated changes in each stage. Results: Cognitive impairment was manifested as early as 2 months age, prior to the identification of tau aggregation and phosphorylation by immunostaining. P301S mice manifested an increased pro-inflammatory related changes at mRNA transcription level (IL-1b and IL17A) with the progression of the disease and when compared to the WT mice of the same age. Among the identified genes in the current study, the nuclear factor (erythroid-derived 2)-like 2 (Nrf2) genes expression that is considered as the master regulator of an endogenous inducible defense system was significantly impaired in P301S mice by 4 and 6 months when compared to healthy WT controls. A data that was also supported by the immunostaining of the serial brain sections including the both brain stem and hippocampus. The current result is suggesting that the downregulation of Nrf2 gene and the impaired Nrf2 dependent anti-inflammatory mechanisms in P301S mice brain is possibly contributing -among other factors- in the neuroinflammation and tauopathy, and that modulation of Nrf2 signaling impairments can be further investigated as a promising potential therapeutic target for tauopathy.
Correction: Effect of VAChT reduction on lung alterations induced by exposure to iron particles in an asthma model.
Dos Santos TM, Righetti RF, do Nascimento Camargo L … +20 more , Leick EA, Fukuzaki S, de Campos EC, Galli TT, Saraiva-Romanholo BM, da Silva LLS, Barbosa JAS, João JMLG, Prado CM, de Rezende BG, Bourotte CLM, Lopes FDTQDS, Martins MA, Bensenor IM, de Oliveira Cirillo JV, Bezerra SKM, Silva FJA, Paulo MSL, Lotufo PA, Tibério IFLC
J Inflamm (Lond) · 2024 Jul · PMID 39080637 · Full text
Abstract loading — click title to view on PubMed.
MAP3K8 is a potential therapeutic target in airway epithelial inflammation.
Chiu CY, Willis-Owen SAG, Wong KCC … +4 more , Farrow SN, Cookson WOC, Moffatt MF, Zhang Y
J Inflamm (Lond) · 2024 Jul · PMID 39030600 · Full text
BACKGROUND: We have previously discovered clusters of sequentially negative and positive modulators of acute inflammation during cytokine stimulation in epithelial cells and identified potential targets for therapy withi...
BACKGROUND: We have previously discovered clusters of sequentially negative and positive modulators of acute inflammation during cytokine stimulation in epithelial cells and identified potential targets for therapy within these clusters. MAP3K8 is a druggable kinase that we found to be a hub of a principal interaction network. We describe here the results of MAP3K8 knockdown in the A549 lung cancer cell line, the BEAS-2B epithelial cell line and normal human bronchial epithelial (NHBE) cells following IL-1β stimulation. We analysed signalling transduction and global gene expression after IL-1β stimulation with and without MAP3K8 knockdown, quantifying levels of the inflammatory cytokines IL-6, IL-8 and RANTES levels by qPCRs and/or by ELISAs. We also examined potential small molecule inhibitors for MAP3K8 in the same models. RESULTS: IL-1β significantly and consistently increased MAP3K8 expression after 2 h in A549, BEAS-2B and NHBE cells. Phosphorylation of MAP3K8 occurred at 20 min after IL-1β stimulation and MAP3K8 protein was degraded at 30 min. MAP3K8 knockdown significantly reduced IL-6, IL-8 levels after IL-1β stimulation and yielded a 10-fold enhancement of the anti-inflammatory effects of dexamethasone. Phosphorylation of ERK1/2 (P-ERK1/2) and phosphorylation of SAPK/JNK (P-SAPK/JNK) decreased at 30 min after IL-1β stimulation with MAP3K8 knockdown. The combination of dexamethasone and MAP3K8 knockdown resulted in greater inhibition of phosphorylated ERK1/2 and SAPK/JNK. Nineteen genes including MMP1, MMP3, MMP10, ITGB8, LAMC2 and PLAT (P corrected < 0.01 respectively) demonstrated a distinct altered temporal response to IL-1β following suppression of MAP3K8. However, putative MAP3K8 inhibitors including Tpl2-1, Tpl2-2 and GSK2222867A only showed inhibition of IL-6 and IL-8 production at a high dose. CONCLUSIONS: These results confirm that MAP3K8 is a key mediator of the early inflammatory response and that it is a potential target in inflammatory diseases. However, current tool compounds do not effectively inhibit its effects.
Emodin alleviates intestinal ischemia-reperfusion injury through antioxidant stress, anti-inflammatory responses and anti-apoptosis effects via Akt-mediated HO-1 upregulation.
Liu Y, Ji T, Jiang H … +4 more , Chen M, Liu W, Zhang Z, He X
J Inflamm (Lond) · 2024 Jul · PMID 38982499 · Full text
BACKGROUND: Intestinal ischemia-reperfusion (I/R) injury is a severe vascular emergency. Previous research indicated the protective effects of Emodin on I/R injury. Our study aims to explore the effect of Emodin on intes...
BACKGROUND: Intestinal ischemia-reperfusion (I/R) injury is a severe vascular emergency. Previous research indicated the protective effects of Emodin on I/R injury. Our study aims to explore the effect of Emodin on intestinal I/R (II/R) injury and elucidate the underlying mechanisms. METHODS: C57BL/6 mice and Caco-2 cells were used for in vivo and in vitro studies. We established an animal model of II/R injury by temporarily occluding superior mesenteric artery. We constructed an oxygen-glucose deprivation/reoxygenation (OGD/R) cell model using a hypoxia-reoxygenation incubator. Different doses of Emodin were explored to determine the optimal therapeutic dose. Additionally, inhibitors targeting the protein kinase B (Akt) or Heme oxygenase-1 (HO-1) were administered to investigate their potential protective mechanisms. RESULTS: Our results demonstrated that in animal experiments, Emodin mitigated barrier disruption, minimized inflammation, reduced oxidative stress, and inhibited apoptosis. When Akt or HO-1 was inhibited, the protective effect of Emodin was eliminated. Inhibiting Akt also reduced the level of HO-1. In cell experiments, Emodin reduced inflammation and apoptosis in the OGD/R cell model. Additionally, when Akt or HO-1 was inhibited, the protective effect of Emodin was weakened. CONCLUSIONS: Our findings suggest that Emodin may protect the intestine against II/R injury through the Akt/HO-1 signaling pathway.
Protective and curative effects of unconjugated bilirubin on gene expression of LOX-1 and iNOS in the heart of rats receiving high-fat diet and low dose streptozotocin: a histomorphometric approach.
Maleki MH, Vakili O, Tavakoli R … +6 more , Nadimi E, Noori Z, Taghizadeh M, Dehghanian A, Tayebi L, Shafiee SM
J Inflamm (Lond) · 2024 Jul · PMID 38982470 · Full text
BACKGROUND: Atherosclerosis is a chronic inflammatory condition affecting the large arteries and is a major cause of cardiovascular diseases (CVDs) globally. Increased levels of adhesion molecules in cardiac tissue serve...
BACKGROUND: Atherosclerosis is a chronic inflammatory condition affecting the large arteries and is a major cause of cardiovascular diseases (CVDs) globally. Increased levels of adhesion molecules in cardiac tissue serve as prognostic markers for coronary artery occlusion risk. Given the antioxidant properties of bilirubin and its inverse correlation with atherosclerosis, this study aimed to assess the beneficial effects of bilirubin on atherosclerotic indices and heart structure in high-fat diet-fed diabetic rats with atherosclerosis. METHODS: Atherosclerosis was induced in three out of five groups of adult male Sprague Dawley rats through a 14-week period of high-fat diet (HFD) consumption and a single low dose of streptozotocin (STZ) (35 mg/kg). The atherosclerotic rats were then treated with intraperitoneal administration of 10 mg/kg/day bilirubin for either 6 or 14 weeks (treated and protected groups, respectively), or the vehicle. Two additional groups served as the control and bilirubin-treated rats. Subsequently, the mRNA expression levels of vascular cell adhesion molecule 1 (VCAM-1), intercellular adhesion molecule 1 (ICAM-1), lectin-like LDL receptor 1 (LOX-1), and the inducible nitric oxide synthase (iNOS) were analyzed using quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR). Histopathological and stereological analyses were performed to assess changes in the heart structure. RESULTS: Bilirubin significantly decreased the expression of VCAM-1, ICAM-1, LOX-1, and iNOS genes in the treated group. Moreover, bilirubin mitigated pathological damage in the left ventricle of the heart. Stereological analysis revealed a decrease in the left ventricle and myocardium volume, accompanied by an increase in vessel volume in rats treated with bilirubin. CONCLUSION: These findings demonstrate that mild hyperbilirubinemia can protect against the progression of atherosclerosis and heart failure by improving lipid profile, modulating adhesion molecules, LOX-1, and iNOS gene expression levels.
Effect of VAChT reduction on lung alterations induced by exposure to iron particles in an asthma model.
Dos Santos TM, Righetti RF, do Nascimento Camargo L … +20 more , Leick EA, Fukuzaki S, de Campos EC, Galli TT, Saraiva-Romanholo BM, da Silva LLS, Barbosa JAS, João JMLG, Prado CM, de Rezende BG, Bourotte CLM, Dos Santos Lopes FDTQ, de Arruda Martins M, Bensenor IM, de Oliveira Cirillo JV, Bezerra SKM, Silva FJA, Paulo MSL, Lotufo PA, Lopes Calvo Tibério IF
J Inflamm (Lond) · 2024 Jul · PMID 38961398 · Full text
INTRODUCTION: Pollution harms the health of people with asthma. The effect of the anti-inflammatory cholinergic pathway in chronic allergic inflammation associated to pollution is poorly understood. METHODS: One hundred...
INTRODUCTION: Pollution harms the health of people with asthma. The effect of the anti-inflammatory cholinergic pathway in chronic allergic inflammation associated to pollution is poorly understood. METHODS: One hundred eight animals were divided into 18 groups (6 animals). Groups included: wild type mice (WT), genetically modified with reduced VAChT (VAChTKD), and those sensitized with ovalbumin (VAChTKDA), exposed to metal powder due to iron pelletizing in mining company (Local1) or 3.21 miles away from a mining company (Local2) in their locations for 2 weeks during summer and winter seasons. It was analyzed for hyperresponsivity, inflammation, remodeling, oxidative stress responses and the cholinergic system. RESULTS: During summer, animals without changes in the cholinergic system revealed that Local1 exposure increased the hyperresponsiveness (%Rrs, %Raw), and inflammation (IL-17) relative to vivarium animals, while animals exposed to Local2 also exhibited elevated IL-17. During winter, animals without changes in the cholinergic system revealed that Local2 exposure increased the hyperresponsiveness (%Rrs) relative to vivarium animals. Comparing the exposure local of these animals during summer, animals exposed to Local1 showed elevated %Rrs, Raw, and IL-5 compared to Local 2, while in winter, Local2 exposure led to more IL-17 than Local1. Animals with VAChT attenuation displayed increased %Rrs, NFkappaB, IL-5, and IL-13 but reduced alpha-7 compared to animals without changes in the cholinergic system WT. Animals with VAChT attenuation and asthma showed increased the hyperresponsiveness, all inflammatory markers, remodeling and oxidative stress compared to animals without chronic lung inflammation. Exposure to Local1 exacerbated the hyperresponsiveness, oxidative stressand inflammation in animals with VAChT attenuation associated asthma, while Local2 exposure led to increased inflammation, remodeling and oxidative stress. CONCLUSIONS: Reduced cholinergic signaling amplifies lung inflammation in a model of chronic allergic lung inflammation. Furthermore, when associated with pollution, it can aggravate specific responses related to inflammation, oxidative stress, and remodeling.
Microcirculatory disturbance in acute liver injury is triggered by IFNγ-CD40 axis.
Kurokawa M, Goya T, Kohjima M … +15 more , Tanaka M, Iwabuchi S, Shichino S, Ueha S, Hioki T, Aoyagi T, Takahashi M, Imoto K, Tashiro S, Suzuki H, Kato M, Hashimoto S, Matsuda H, Matsushima K, Ogawa Y
J Inflamm (Lond) · 2024 Jun · PMID 38907339 · Full text
BACKGROUND: Acute liver failure (ALF) is a life-threatening disorder that progresses from self-limiting acute liver injury (ALI). Microcirculatory disturbance characterized by sinusoidal hypercoagulation and subsequent m...
BACKGROUND: Acute liver failure (ALF) is a life-threatening disorder that progresses from self-limiting acute liver injury (ALI). Microcirculatory disturbance characterized by sinusoidal hypercoagulation and subsequent massive hypoxic hepatocyte damage have been proposed to be the mechanism by which ALI deteriorates to ALF; however, the precise molecular pathway of the sinusoidal hypercoagulation remains unknown. Here, we analyzed ALI patients and mice models to uncover the pathogenesis of ALI with microcirculatory disturbance. METHODS: We conducted a single-center retrospective study for ALI and blood samples and liver tissues were analyzed to evaluate the microcirculatory disturbance in ALI patients (n = 120). Single-cell RNA sequencing analysis (scRNA-seq) was applied to the liver from the concanavalin A (Con A)‑induced mouse model of ALI. Interferon-gamma (IFNγ) and tumor necrosis factor-alpha knockout mice, and primary human liver sinusoidal endothelial cells (LSECs) were used to assess the mechanism of microcirculatory disturbance. RESULTS: The serum IFNγ concentrations were significantly higher in ALI patients with microcirculatory disturbance than in patients without microcirculatory disturbance, and the IFNγ was upregulated in the Con A mouse model which presented microcirculatory disturbance. Hepatic IFNγ expression was increased as early as 1 hour after Con A treatment prior to sinusoidal hypercoagulation and hypoxic liver damage. scRNA-seq revealed that IFNγ was upregulated in innate lymphoid cells and stimulated hepatic vascular endothelial cells at the early stage of liver injury. In IFNγ knockout mice treated with Con A, the sinusoidal hypercoagulation and liver damage were remarkably attenuated, concomitant with the complete inhibition of CD40 and tissue factor (TF) upregulation in vascular endothelial cells. By ligand-receptor analysis, CD40-CD40 ligand interaction was identified in vascular endothelial cells. In human LSECs, IFNγ upregulated CD40 expression and TF was further induced by increased CD40-CD40 ligand interaction. Consistent with these findings, hepatic CD40 expression was significantly elevated in human ALI patients with microcirculatory disturbance. CONCLUSION: We identified the critical role of the IFNγ-CD40 axis as the molecular mechanism of microcirculatory disturbance in ALI. This finding may provide novel insights into the pathogenesis of ALI and potentially contribute to the emergence of new therapeutic strategies for ALI patients.
YTHDC1 inhibits autophagy-dependent NF-κB signaling by stabilizing Beclin1 mRNA in macrophages.
Zhou L, Zhang L, Lv Y … +3 more , Qian J, Huang L, Qu C
J Inflamm (Lond) · 2024 Jun · PMID 38877444 · Full text
BACKGROUND: YTHDC1, a key m(6)A nuclear reader, plays a crucial role in regulating mRNA splicing, export, and stability. However, the functional significance and regulatory mechanisms of YTHDC1 in inflammatory bowel dise...
BACKGROUND: YTHDC1, a key m(6)A nuclear reader, plays a crucial role in regulating mRNA splicing, export, and stability. However, the functional significance and regulatory mechanisms of YTHDC1 in inflammatory bowel disease (IBD) remain to be explored. METHODS: We established a dextran sulfate sodium (DSS)-induced murine colitis model in vivo and LPS/IFN-γ-stimulated macrophage inflammation in vitro. The expression of YTHDC1 was determined. Colocalization of YTHDC1 and macrophages was assayed by immunofluorescence staining. LV-YTHDC1 or shYTHDC1 lentiviruses were applied for YTHDC1 overexpression or inhibition. For NF-κB inhibition, JSH-23 was utilized. The interaction of YTHDC1 and Beclin1 mRNA was determined by RIP, and the m6A modification of Beclin1 was confirmed by MeRIP. RESULTS: In DSS-induced colitis and LPS/IFN-γ-treated RAW264.7 macrophages, we observed a significant downregulation of YTHDC1. Overexpression of YTHDC1 resulted in decreased levels of iNOS, CD86, and IL-6 mRNA, along with inhibited NF-κB activation in LPS/IFN-γ-treated RAW264.7 cells. Conversely, downregulation of YTHDC1 promoted iNOS expression and inhibited autophagy. Additionally, the effect of YTHDC1 knockdown on CD86 and IL-6 mRNA induced by LPS/IFN-γ was abolished by the NF-κB inhibitor JSH-23. Mechanistically, YTHDC1 interacted with Beclin1 mRNA, thereby stabilizing Beclin1 mRNA and enhancing Beclin1 expression and autophagy. These effects ultimately led to the inhibition of NF-κB signaling in LPS/IFN-γ-challenged macrophages. CONCLUSIONS: YTHDC1 inhibited the macrophage-mediated inflammatory response by stabilizing Beclin1 mRNA, which may be a potential therapeutic target for the treatment of IBD.
Correction: Inhibition of GSK3β activity alleviates acute liver failure via suppressing multiple programmed cell death.
Zhang D, Shi C, Zhang Q … +3 more , Wang Y, Guo J, Gong Z
J Inflamm (Lond) · 2024 Jun · PMID 38867290 · Full text
Abstract loading — click title to view on PubMed.
Therapeutic potential of exosomes derived from mesenchymal stem cells for treatment of systemic lupus erythematosus.
Samavati SF, Yarani R, Kiani S … +7 more , HoseinKhani Z, Mehrabi M, Levitte S, Primavera R, Chetty S, Thakor AS, Mansouri K
J Inflamm (Lond) · 2024 Jun · PMID 38867277 · Full text
Autoimmune diseases are caused by an imbalance in the immune system, producing autoantibodies that cause inflammation leading to tissue damage and organ dysfunction. Systemic Lupus Erythematosus (SLE) is one of the most...
Autoimmune diseases are caused by an imbalance in the immune system, producing autoantibodies that cause inflammation leading to tissue damage and organ dysfunction. Systemic Lupus Erythematosus (SLE) is one of the most common autoimmune diseases and a major contributor to patient morbidity and mortality. Although many drugs manage the disease, curative therapy remains elusive, and current treatment regimens have substantial side effects. Recently, the therapeutic potential of exosomes has been extensively studied, and novel evidence has been demonstrated. A direct relationship between exosome contents and their ability to regulate the immune system, inflammation, and angiogenesis. The unique properties of extracellular vesicles, such as biomolecule transportation, biodegradability, and stability, make exosomes a promising treatment candidate for autoimmune diseases, particularly SLE. This review summarizes the structural features of exosomes, the isolation/purification/quantification method, their origin, effect, immune regulation, a critical consideration for selecting an appropriate source, and their therapeutic mechanisms in SLE.
The anti-inflammatory properties of vinpocetine mediates its therapeutic potential in management of atherosclerosis.
Alshehri AA, Al-Kuraishy HM, Al-Gareeb AI … +7 more , Jawad SF, Khawagi WY, Alexiou A, Papadakis M, Assiri AA, Elhadad H, El-Saber Batiha G
J Inflamm (Lond) · 2024 Jun · PMID 38858751 · Full text
Atherosclerosis (AS) formation is enhanced by different mechanisms including cytokine generation, vascular smooth muscle cell proliferation, and migration. One of the recent treatments towards endothelial dysfunction and...
Atherosclerosis (AS) formation is enhanced by different mechanisms including cytokine generation, vascular smooth muscle cell proliferation, and migration. One of the recent treatments towards endothelial dysfunction and AS is Vinpocetine (VPN). VPN is a potent inhibitor of phosphodiesterase enzyme 1 (PDE-1) and has anti-inflammatory and antioxidant effects through inhibition the expression of nuclear factor kappa B (NF-κB). VPN has been shown to be effective against the development and progression of AS. However, the underlying molecular mechanism was not fully clarified. Consequently, objective of the present review was to discuss the mechanistic role of VPN in the pathogenesis AS. Most of pro-inflammatory cytokines that released from macrophages are inhibited by action of VPN through NF-κB-dependent mechanism. VPN blocks monocyte adhesion and migration by constraining the expression and action of pro-inflammatory cytokines. As well, VPN is effective in reducing of oxidative stress a cornerstone in the pathogenesis of AS through inhibition of NF-κB and PDE1. VPN promotes plaque stability and prevents the erosion and rupture of atherosclerotic plaque. In conclusion, VPN through mitigation of inflammatory and oxidative stress, and improvement of plaque stability effects could be effective agent in the management of AS.
Cinnamaldehyde inhibits the NLRP3 inflammasome by preserving mitochondrial integrity and augmenting autophagy in Shigella sonnei-infected macrophages.
Hua KF, Lin YB, Chiu HW … +9 more , Wong WT, Ka SM, Wu CH, Lin WY, Wang CC, Hsu CH, Hsu HT, Ho CL, Li LH
J Inflamm (Lond) · 2024 Jun · PMID 38840105 · Full text
BACKGROUND: Worldwide, more than 125 million people are infected with Shigella each year and develop shigellosis. In our previous study, we provided evidence that Shigella sonnei infection triggers activation of the NACH...
BACKGROUND: Worldwide, more than 125 million people are infected with Shigella each year and develop shigellosis. In our previous study, we provided evidence that Shigella sonnei infection triggers activation of the NACHT, LRR, and PYD domain-containing protein 3 (NLRP3) inflammasome in macrophages. NLRP3 inflammasome is responsible for regulating the release of the proinflammatory cytokines interleukin (IL)-1β and IL-18 through the protease caspase-1. Researchers and biotech companies have shown great interest in developing inhibitors of the NLRP3 inflammasome, recognizing it as a promising therapeutic target for several diseases. The leaves of Cinnamomum osmophloeum kaneh, an indigenous tree species in Taiwan, are rich in cinnamaldehyde (CA), a compound present in significant amounts. Our aim is to investigate how CA affects the activation of the NLRP3 inflammasome in S. sonnei-infected macrophages. METHODS: Macrophages were infected with S. sonnei, with or without CA. ELISA and Western blotting were employed to detect protein expression or phosphorylation levels. Flow cytometry was utilized to assess HO production and mitochondrial damage. Fluorescent microscopy was used to detect cathepsin B activity and mitochondrial ROS production. Additionally, colony-forming units were employed to measure macrophage phagocytosis and bactericidal activity. RESULTS: CA inhibited the NLRP3 inflammasome in S. sonnei-infected macrophages by suppressing caspase-1 activation and reducing IL-1β and IL-18 expression. CA also inhibited pyroptosis by decreasing caspase-11 and Gasdermin D activation. Mechanistically, CA reduced lysosomal damage and enhanced autophagy, while leaving mitochondrial damage, mitogen-activated protein kinase phosphorylation, and NF-κB activation unaffected. Furthermore, CA significantly boosted phagocytosis and the bactericidal activity of macrophages against S. sonnei, while reducing secretion of IL-6 and tumour necrosis factor following infection. CONCLUSION: CA shows promise as a nutraceutical for mitigating S. sonnei infection by diminishing inflammation and enhancing phagocytosis and the bactericidal activity of macrophages against S. sonnei.
Lipopolysaccharide pretreatment increases the sensitivity of the TRPV1 channel and promotes an anti-inflammatory phenotype of capsaicin-activated macrophages.
Vašek D, Fikarová N, Marková VN … +7 more , Honc O, Pacáková L, Porubská B, Somova V, Novotný J, Melkes B, Krulová M
J Inflamm (Lond) · 2024 May · PMID 38790047 · Full text
BACKGROUND: The transient receptor potential vanilloid 1 (TRPV1) is well-established in neuronal function, yet its role in immune reactions remains enigmatic. The conflicting data on its inflammatory role, suggesting bot...
BACKGROUND: The transient receptor potential vanilloid 1 (TRPV1) is well-established in neuronal function, yet its role in immune reactions remains enigmatic. The conflicting data on its inflammatory role, suggesting both pro-inflammatory and anti-inflammatory effects upon TRPV1 stimulation in immune cells, adds complexity. To unravel TRPV1 immunomodulatory mechanisms, we investigated how the TRPV1 agonist capsaicin influences lipopolysaccharide (LPS)-induced pro-inflammatory macrophage phenotypes. RESULTS: Changes in the surface molecules, cytokine production, and signaling cascades linked to the phenotype of M1 or M2 macrophages of the J774 macrophage cell line and bone marrow-derived macrophages, treated with capsaicin before or after the LPS-induced inflammatory reaction were determined. The functional capacity of macrophages was also assessed by infecting the stimulated macrophages with the intracellular parasite Leishmania mexicana. CONCLUSION: Our findings reveal that TRPV1 activation yields distinct macrophage responses influenced by the inflammatory context. LPS pre-treatment followed by capsaicin activation prompted increased calcium influx, accompanied by a shift toward an anti-inflammatory M2b-like polarization state.
About
- Frequency
- Sun
- Papers found
- 200
- RSS feed
- Subscribe