Lipoxin A4-Mediated p38 MAPK Signaling Pathway Protects Mice Against Collagen-Induced Arthritis
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Lipoxin A4‑Mediated p38 MAPK Signaling Pathway Protects Mice Against Collagen‑Induced Arthritis Jinyu Li1 · Qi Sun1 · Chenying Zheng1 · Chunxiao Bai1 · Chuyin Liu1 · Xueqian Zhao1 · Peiying Deng2 · Limin Chai2 · Yusong Jia1 Received: 5 September 2019 / Accepted: 12 November 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract The aim of the article was to study the mechanism of Lipoxin A4 (LXA4)-mediated p38 MAPK pathway protecting mice against collagen-induced arthritis (CIA). The impact of LXA4 (0, 5, 10, 15 nM) on synoviocytes proliferation of CIA mice was detected using 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. CIA mice were treated with LXA4, SB203580 (a p38 inhibitor), and/ or anisomycin (a p38 agonist), and the arthritis severity score in each mouse was determined. The gene or protein expressions were detected with Western Blotting, ELISA, or qRT-PCR. LXA4 inhibited the synoviocytes proliferation of CIA mice with decreased levels of TNF-α, IL-6, IL-1β, and IFN-γ and reduced p-p38/total p38 expression in synoviocytes in a dose-dependent manner. LXA4 levels were decreased in synovial tissues and plasma of CIA mice, but p-p38/total p38 expression was increased in synovial tissues. LXA4 could downregulate p-p38/total p38 expression in synovial tissues of CIA mice. Both LXA4 and SB203580 reduced arthritis severity score of CIA mice with the reduction of synovial tissue hyperplasia and inflammatory cell infiltration. CIA mice treated with LXA4 and SB203580 had lower levels of TNF-α, IL-6, IL-1β, and IFN-γ, accompanying decreased MDA as well as increased SOD, CAT,and GPx. However, anisomycin could reverse the protect effects of LXA4 on CIA mice regarding the abovementioned inflammatory factors and oxidative stress indexes. LXA4 protected mice against collagen-induced arthritis via inhibiting p38 MAPK signaling pathway, which may be a potential new therapeutic target for rheumatoid arthritis.
Jinyu Li and Qi Sun are co-first authors. * Limin Chai [email protected] * Yusong Jia [email protected] Extended author information available on the last page of the article
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Biochemical Genetics
Keywords Lipoxin A4 · Collagen-induced arthritis · p38 MAPK · Rheumatoid arthritis
Introduction Rheumatoid arthritis (RA) is a common systemic autoimmune disease, with various extra-articular manifestations (Zerbini et al. 2017). The typical symptom of RA is symmetrical chronic polyarticular synovitis of the diarthrodial joints, eventually leading to structural damage of joints due to persistent progression and recurrence (Derk 2005; Okada et al. 2010). According to statistical reports, the morbidity was approximately 0.24% worldwide, 0.3% to 1% in developed countries, and 0.28% in China (An et al. 2017). Extensive and intensive studies on RA have been conducted for many years, but the pathogenesis is still unclear, and the effect of treatment is unsatisfactory. Therefore, scholars at home and abroad established animal models to explor
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