4.4 Article

Lipoxin A4-Mediated p38 MAPK Signaling Pathway Protects Mice Against Collagen-Induced Arthritis

期刊

BIOCHEMICAL GENETICS
卷 59, 期 1, 页码 346-365

出版社

SPRINGER/PLENUM PUBLISHERS
DOI: 10.1007/s10528-020-10016-9

关键词

Lipoxin A4; Collagen-induced arthritis; p38 MAPK; Rheumatoid arthritis

资金

  1. Beijing University of Traditional Chinese Medicine Dongzhimen Hospital Youth Talent Project [DZMYY-201802]
  2. Chinese Traditional Medicine Association Young Talents Lifting Project [NQRC2-C08]

向作者/读者索取更多资源

This study found that LXA4 could protect CIA mice by inhibiting p38 MAPK pathway, reducing synoviocyte proliferation, decreasing inflammatory cytokine levels, alleviating oxidative stress, and easing arthritis severity.
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-alpha, IL-6, IL-1 beta, and IFN-gamma 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-alpha, IL-6, IL-1 beta, and IFN-gamma, 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.

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