CXCL1 contributes to IL-6 expression in osteoarthritis and rheumatoid arthritis synovial fibroblasts by CXCR2, c-Raf, MAPK, and AP-1 pathway

Hou, Sheng; Chen, Po Chun; Lin, Chieh Mo; Ma, Fang; Ching, Miao; Liu, Ju-Fang

doi:10.1186/s13075-020-02331-8

Cited by 49 publications

(39 citation statements)

References 57 publications

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“… 30 Meanwhile, evidence shows that activation of AP-1 is related to the production of pro-inflammatory cytokines in RA. 31 In the present study, we found that the expressions of p65, c-Jun, and c-Fos were significant in IL-18-induced FLS. Our data demonstrates that roflumilast has a strong inhibitory effect on the activation of NF-κB and AP-1.…”

Section: Discussionsupporting

confidence: 55%

Roflumilast Reduced the IL-18-Induced Inflammatory Response in Fibroblast-Like Synoviocytes (FLS)

Zhong¹,

Guo²,

Yang

et al. 2021

ACS Omega

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Pro-inflammatory cytokines, such as the IL-18-induced inflammatory response and associated damage in fibroblast-like synoviocytes (FLS), play an important role in the pathogenesis of rheumatoid arthritis (RA). Roflumilast, an inhibitor of phosphodiesterase-4 (PDE-4), has been licensed for the treatment of chronic obstructive pulmonary disease (COPD). However, it is unknown whether roflumilast possesses a protective effect against the IL-18-induced inflammatory response in FLS. We found that roflumilast attenuated IL-18-induced oxidative stress by reducing the production of reactive oxygen species and malondialdehyde (MDA) in MH7A fibroblast-like synoviocytes (FLS). Additionally, roflumilast prevented IL-18-induced expressions and secretions of pro-inflammatory cytokines such as IL-6, IL-8, and TNF-α. Importantly, we found that roflumilast inhibited IL-18-induced expressions of chemokines such as CCL5, CXCL9, and CXCL10. Further, roflumilast inhibited the expression of extracellular matrix degradative enzymes, such as matrix metalloproteinase-3 (MMP-3) and MMP-13. Mechanistically, we found that roflumilast suppressed the activation of the transcriptional factor AP-1 and NF-κB. Our results suggest that roflumilast might be a potential therapeutic agent for the treatment of RA.

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Section: Discussionsupporting

confidence: 55%

Roflumilast Reduced the IL-18-Induced Inflammatory Response in Fibroblast-Like Synoviocytes (FLS)

Zhong¹,

Guo²,

Yang

et al. 2021

ACS Omega

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“…The chemokines CXCL1, CXCL5, and CXCL6, known for their neutrophil chemoattractant effects at the site of injury, infection, or inflammation ( 21 ), decreased significantly in the main analysis. In studies on synovial fibroblasts isolated from patients with RA, CXCL1 is indicated to stimulate an inflammatory response and upregulate IL-6 expression ( 22 ). Previously, higher concentration of CXCL1 was reported in plasma and synovial fluids from patients with RA compared with healthy volunteers, and CXCL1 is thus suggested to play a mediating role in neutrophil recruitment into the inflamed joint ( 23 ).…”

Section: Discussionmentioning

confidence: 99%

Proposed Anti-Inflammatory Diet Reduces Inflammation in Compliant, Weight-Stable Patients with Rheumatoid Arthritis in a Randomized Controlled Crossover Trial

Hulander

Bärebring

Wadell

et al. 2021

The Journal of Nutrition

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Background It is unclear to what extent adjuvant dietary intervention can influence inflammation in rheumatoid arthritis (RA). Objectives The objective was to assess the effects of dietary manipulation on inflammation in patients with RA. Methods In a crossover design, participants [n = 50, 78% females, median BMI (in kg/m2) 27, median age 63 y] were randomly assigned to begin with either a 10-wk portfolio diet of proposed anti-inflammatory foods (i.e., a high intake of fatty fish, whole grains, fruits, nuts, and berries) or a control diet resembling a Western diet with a 4-mo washout in between. This report evaluates the secondary outcome markers of inflammation among participants with stable medication. Analyses were performed using a linear mixed ANCOVA model. Results There were no significant effects on CRP or ESR in the group as a whole. In those with high compliance (n = 29), changes in ESR within the intervention diet period differed significantly compared with changes within the control diet period (mean: –5.490; 95% CI: –10.310, –0.669; P = 0.027). During the intervention diet period, there were lowered serum concentrations of C-X-C motif ligand 1 (CXCL1) (mean: –0.268; 95% CI: –0.452, –0.084;P = 0.006), CXCL5 (mean: –0.278; 95% CI: –0.530, –0.026 P = 0.031), CXCL6 (mean: –0.251; 95% CI: –0.433, –0.069; P = 0.009), and tumor necrosis factor ligand superfamily member 14 (TNFSF14) (mean: –0.139; 95% CI: –0.275, –0.002; P = 0.047) compared with changes within the control diet period. Conclusion A proposed anti-inflammatory diet likely reduced systemic inflammation, as indicated by a decreased ESR in those who completed the study with high compliance (n = 29). These findings warrant further studies to validate our results, and to evaluate the clinical relevance of changes in CXCL1, CXCL5, CXCL6, and TNFSF14 in patients with RA.

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“…It may be possible that the constant monotone mechanical strain of advanced amplitude is required to sustain cytokine depletion. While under usage (SM) of the TMJ seemed to support angiogenesis and wound healing processes by increased Cxcl-1 levels [ 60 ], the TMJ seemed to benefit from mechanical loaded synovial fibroblasts by the depleted proinflammatory cytokine expression.…”

Section: Discussionmentioning

confidence: 99%

Mechanical Stress Induce PG-E2 in Murine Synovial Fibroblasts Originating from the Temporomandibular Joint

Nazet

Feulner

Neubert

et al. 2021

Cells

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Genetic predisposition, traumatic events, or excessive mechanical exposure provoke arthritic changes in the temporomandibular joint (TMJ). We analysed the impact of mechanical stress that might be involved in the development and progression of TMJ osteoarthritis (OA) on murine synovial fibroblasts (SFs) of temporomandibular origin. SFs were subjected to different protocols of mechanical stress, either to a high-frequency tensile strain for 4 h or to a tensile strain of varying magnitude for 48 h. The TMJ OA induction was evaluated based on the gene and protein secretion of inflammatory factors (Icam-1, Cxcl-1, Cxcl-2, Il-1ß, Il-1ra, Il-6, Ptgs-2, PG-E2), subchondral bone remodelling (Rankl, Opg), and extracellular matrix components (Col1a2, Has-1, collagen and hyaluronic acid deposition) using RT-qPCR, ELISA, and HPLC. A short high-frequency tensile strain had only minor effects on inflammatory factors and no effects on the subchondral bone remodelling induction or matrix constituent production. A prolonged tensile strain of moderate and advanced magnitude increased the expression of inflammatory factors. An advanced tensile strain enhanced the Ptgs-2 and PG-E2 expression, while the expression of further inflammatory factors were decreased. The tensile strain protocols had no effects on the RANKL/OPG expression, while the advanced tensile strain significantly reduced the deposition of matrix constituent contents of collagen and hyaluronic acid. The data indicates that the application of prolonged advanced mechanical stress on SFs promote PG-E2 protein secretion, while the deposition of extracellular matrix components is decreased.

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CXCL1 contributes to IL-6 expression in osteoarthritis and rheumatoid arthritis synovial fibroblasts by CXCR2, c-Raf, MAPK, and AP-1 pathway

Cited by 49 publications

References 57 publications

Roflumilast Reduced the IL-18-Induced Inflammatory Response in Fibroblast-Like Synoviocytes (FLS)

Roflumilast Reduced the IL-18-Induced Inflammatory Response in Fibroblast-Like Synoviocytes (FLS)

Proposed Anti-Inflammatory Diet Reduces Inflammation in Compliant, Weight-Stable Patients with Rheumatoid Arthritis in a Randomized Controlled Crossover Trial

Mechanical Stress Induce PG-E2 in Murine Synovial Fibroblasts Originating from the Temporomandibular Joint

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