scholarly journals Soluble CD14 Induces Pro-inflammatory Cytokines in Rheumatoid Arthritis Fibroblast-Like Synovial Cells via Toll-Like Receptor 4

Cells ◽  
2020 ◽  
Vol 9 (7) ◽  
pp. 1689
Author(s):  
Yoshihide Ichise ◽  
Jun Saegusa ◽  
Shino Tanaka-Natsui ◽  
Ikuko Naka ◽  
Shinya Hayashi ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Inflammatory Cytokines ◽  
Intercellular Adhesion Molecule ◽  
Toll Like Receptor ◽  
Intercellular Adhesion Molecule 1 ◽  
Toll Like Receptor 4 ◽  
Soluble Cd14 ◽  
Mrna Induction ◽  
Tnf Α ◽  
Pro Inflammatory Cytokines

Objectives: Synovial fluids of rheumatoid arthritis (RA) patients commonly contain high concentrations of soluble CD14 (sCD14). To investigate its potential role in RA pathogenesis, we tested whether sCD14 binding transmits a signal to fibroblast-like synoviocytes from RA patients (RA-FLS). Methods: The induction of pro-inflammatory cytokines, chemokines, and mediators by sCD14 stimulation of RA-FLS was quantified by real-time PCR and ELISA. Cell proliferation was assessed by the BrdU assay. LPS-RS, a Toll-like receptor 4 (TLR-4) antagonist, was used to block TLR-4 signaling. Results: Soluble CD14 induced the expression of IL-6 mRNA and secretion of the protein. The expression of other pro-inflammatory cytokines and mediators, such as TNF-α, IL-8, intercellular adhesion molecule-1 (ICAM-1), MMP-3, and RANK ligand (RANKL), was also induced by sCD14. In addition, sCD14 stimulation promoted RA-FLS proliferation. LPS-RS abolished IL-6, IL-8, and ICAM-1 mRNA induction by sCD14 in RA-FLS. On the other hand, TNF-α and IL-17A increased TLR-4 expression by RA-FLS and amplified their sCD14-induced IL-6 expression. Conclusions: Soluble CD14 transmits inflammatory signals to RA-FLS via TLR-4. The effects of sCD14 may be augmented in inflammatory milieu. Our results suggest that sCD14 is involved in the pathogenesis of RA and may be a novel therapeutic target.

scholarly journals Protective effect of naringenin against experimental colitis via suppression of Toll-like receptor 4/NF-κB signalling

2013 ◽  
Vol 110 (4) ◽  
pp. 599-608 ◽  
Author(s):  
Wei Dou ◽  
Jingjing Zhang ◽  
Aning Sun ◽  
Eryun Zhang ◽  
Lili Ding ◽  
...  
Keyword(s):  
Protective Effect ◽  
Intestinal Inflammation ◽  
Nuclear Translocation ◽  
Experimental Colitis ◽  
Intercellular Adhesion Molecule ◽  
Luciferase Expression ◽  
Toll Like Receptor ◽  
Intercellular Adhesion Molecule 1 ◽  
Toll Like Receptor 4 ◽  
Tnf Α

Naringenin, one of the most abundant flavonoids in citrus, grapefruits and tomatoes, has been used as a traditional anti-inflammatory agent for centuries. However, the molecular mechanism of naringenin in intestinal inflammation remains unknown so far. The present study investigated a molecular basis for the protective effect of naringenin in dextran sulphate sodium-induced murine colitis. Pre-administration of naringenin significantly reduced the severity of colitis and resulted in down-regulation of pro-inflammatory mediators (inducible NO synthase (iNOS), intercellular adhesion molecule-1 (ICAM-1), monocyte chemoattractant protein-1 (MCP-1), cyclo-oxygenase-2 (Cox2), TNF-α and IL-6 mRNA) in the colon mucosa. The decline in the production of pro-inflammatory cytokines, specifically TNF-α and IL-6, correlated with a decrease in mucosal Toll-like receptor 4 (TLR4) mRNA and protein. Phospho-NF-κB p65 protein was significantly decreased, which correlated with a similar decrease in phospho-IκBα protein. Consistent with the in vivo results, naringenin exposure blocked lipopolysaccharide-stimulated nuclear translocation of NF-κB p65 in mouse macrophage RAW264.7 cells. In addition, in vitro NF-κB reporter assays performed on human colonic HT-29 cells exposed to naringenin demonstrated a significant inhibition of TNF-α-induced NF-κB luciferase expression. Thus, for the first time, the present study indicates that targeted inhibition of the TLR4/NF-κB signalling pathway might be an important mechanism for naringenin in abrogating experimental colitis.

Toll‐like receptor 4 polymorphisms were associated with low serum pro‐inflammatory cytokines in BCG osteitis survivors

2019 ◽  
Vol 109 (7) ◽  
pp. 1417-1422 ◽  
Author(s):  
Matti Korppi ◽  
Johanna Teräsjärvi ◽  
Eero Lauhkonen ◽  
Heini Huhtala ◽  
Kirsi Nuolivirta ◽  
...  
Keyword(s):  
Inflammatory Cytokines ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4 ◽  
Low Serum ◽  
Pro Inflammatory Cytokines

Effects of local lipopolysaccharide administration on the expression of Toll-like receptor 4 and pro-inflammatory cytokines in uterus and oviduct of rabbit does

2018 ◽  
Vol 107 ◽  
pp. 162-174 ◽  
Author(s):  
Laura Menchetti ◽  
Olimpia Barbato ◽  
Iulia Elena Filipescu ◽  
Giovanna Traina ◽  
Leonardo Leonardi ◽  
...  
Keyword(s):  
Inflammatory Cytokines ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4 ◽  
Pro Inflammatory Cytokines

Over-expression of PTEN attenuates the inflammation of fibroblast-like synoviocytes in rheumatoid arthritis

2020 ◽  
Author(s):  
Xiao-Feng Li ◽  
Qing-Qing Xu ◽  
Man-Wen Yang ◽  
He Chen ◽  
Su-Qin Yin ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Dna Methylation ◽  
Inflammatory Cytokines ◽  
Pten Expression ◽  
Over Expression ◽  
Tnf Α ◽  
And Migration ◽  
Fibroblast Like Synoviocytes ◽  
Pro Inflammatory Cytokines

Abstract Background: Rheumatoid arthritis (RA) is characterized by a tumor-like expansion of the synovium and the subsequent destruction of adjacent articular cartilage and bone. Recent studies have shown that phosphatase and tension homolog deleted on chromosome 10 (PTEN) might contribute to the survival of fibroblast-like synoviocytes (FLS) and the production of pro-inflammatory cytokines in RA.Methods : The expression was determined in RA and adjuvant-induced arthritis (AIA) synovial tissues by immunohistochemistry. FLSs were treatment with bpv, PTEN-RNAi or over-expression plasmid in RA and AIA. FLSs migration was assessed. The ad-PTEN was also injected into the knee of AIA in vivo. Chromatin Immunoprecipitation (ChIP) and Methylation-special PCR (MSP) assay were used to study the expression of PTEN mRNA in DNA methylation.Results : Down-regulated level of PTEN expression was observed in RA and AIA. Inhibition PTEN expression by bpv or PTEN-RNAi could promote the expression of pro-inflammatory cytokines, chemokines and migration of FLS with TNF-α in RA and AIA. Consistently, over-expression of PTEN reduced their low-expression of pro-inflammatory cytokines, chemokines and migration. Intra-articular injection of ad-PTEN in AIA knees dramatically reduced inflammatory and paw swelling in vivo. The ChIP and MSP assay has clearly detected the DNA methylation of PTEN was increased in FLS with TNF-α. Moreover, intraperitoneally injected 5-Aza in AIA also suppressed the inflammatory and paws swelling in vivo.Conclusions: Our findings suggest that over-expression PTEN attenuates the formation of pro-inflammatory cytokines, chemokines and migration of FLS, and it may be regulated by DNA methylation in the pathogenesis of RA.

scholarly journals Effects of Adipose-Derived Biogenic Nanoparticle-Associated microRNA-451a on Toll-like Receptor 4-Induced Cytokines

Pharmaceutics ◽  
2021 ◽  
Vol 14 (1) ◽  
pp. 16
Author(s):  
Xinghua Wang ◽  
Anthony Pham ◽  
Lu Kang ◽  
Sierra A. Walker ◽  
Irina Davidovich ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Signaling Pathways ◽  
Extracellular Vesicles ◽  
Inflammatory Cytokines ◽  
Stromal Cells ◽  
Toll Like Receptor ◽  
Immunomodulatory Effects ◽  
Toll Like Receptor 4 ◽  
Biogenic Nanoparticles ◽  
Pro Inflammatory Cytokines

Extracellular vesicles (EVs) are cell-released nanoparticles that transfer biomolecular content between cells. Among EV-associated biomolecules, microRNAs (miRNAs/miRs) represent one of the most important modulators of signaling pathways in recipient cells. Previous studies have shown that EVs from adipose-derived mesenchymal stromal cells (MSCs) and adipose tissue modulate inflammatory pathways in macrophages. In this study, the effects of miRNAs that are abundant in adipose tissue EVs and other biogenic nanoparticles (BiNPs) were assessed in terms of altering Toll-like receptor 4 (TLR4)-induced cytokines. TLR-4 signaling in macrophages is often triggered by pathogen or damage-induced inflammation and is associated with several diseases. This study demonstrates that miR-451a, which is abundant in adipose tissue BiNPs, suppresses pro-inflammatory cytokines and increases anti-inflammatory cytokines associated with the TLR4 pathway. Therefore, miR-451a may be partially responsible for immunomodulatory effects of adipose tissue-derived BiNPs.

scholarly journals The Expression of Toll-Like Receptor 4 mRNA in PBMCs Is Upregulated in Smokers and Decreases Upon Smoking Cessation

2021 ◽  
Vol 12 ◽  
Author(s):  
Hsin-Yu Yeh ◽  
Shou-Hung Hung ◽  
Su-Chiu Chen ◽  
Fei-Ran Guo ◽  
Hsien-Liang Huang ◽  
...  
Keyword(s):  
Smoking Cessation ◽  
Cigarette Smoking ◽  
Mrna Expression ◽  
Mononuclear Cells ◽  
Intercellular Adhesion Molecule ◽  
Mrna Levels ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4 ◽  
Tlr4 Mrna ◽  
Tnf Α

BackgroundStudies have shown in vitro that cigarette smoke condensate stimulates monocytes to express toll-like receptor 4 (TLR4), tumor necrosis factor-α (TNF-α), and intercellular adhesion molecule 1 (ICAM-1), and enhances their adhesion to the endothelium. However, the same effects of cigarette smoking have not been explored in vivo. This study is to investigate the effect of cigarette smoking and smoking cessation on their mRNA expression in human peripheral blood mononuclear cells (PBMCs).MethodsA group of 97 smokers and 62 nonsmokers were enrolled. The RNA from PBMCs was assessed with real-time polymerase chain reaction (PCR) to determine the levels of ICAM-1, TNF-α, and TLR4. The same markers in PBMCs of 87 quitters were examined before and at one week, one month, and two months after smoking cessation.ResultsOf the 97 smokers, 85 (87.6%) were males, and 30 (48.4%) of the nonsmokers were males (p < 0.0001). The mean (SD) age of the smokers was 43.24 (10.89) years, which was younger than 43.45 (11.41) years of nonsmokers (p < 0.0001). The incidence of cardiovascular diseases was 13.4% in smokers, which was higher than 1.6% in nonsmokers (p < 0.05). Both ICAM-1 and TNF-α mRNA levels in PBMCs were higher among the smokers (p < 0.0001). In addition, TLR4 mRNA levels in PBMCs were statistically elevated in the smokers (p < 0.0001) comparing with those in the nonsmokers. The mRNA levels of TLR4 and TNF-α in PBMCs decreased in those who had quit smoking for 2 months (p < 0.0001).ConclusionsICAM-1, TNF-α, and TLR4 mRNA expression levels in PBMCs increased in smokers and decreased after being on a smoking cessation program for 2 months. This finding suggested that TLR4 expression may mediate the atherogenic inflammatory process induced by smoking.

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