Journal
JOINT BONE SPINE
Volume 83, Issue 5, Pages 525-532Publisher
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.jbspin.2015.09.002
Keywords
JAK inhibitor; Adjuvant-induced arthritis; Th17; Treg; Memory B cells; STAT3
Categories
Funding
- National Nature Science Foundation of China [81330081, 81302784, 81302845, 31200675, 81473223]
- China Postdoctoral Science Foundation [2013M540509]
- Grants for Scientific Research of BSKY from Anhui Medical University [XJ201428]
Ask authors/readers for more resources
Objective: To investigate the effects of JAK inhibitor (SHR0302) on adjuvant-induced arthritis (AA) rats and the partial mechanisms focused on T, B lymphocyte subsets through JAK1-STAT3 pathway, including Th17, Treg, total B cells and memory B cells. Methods: Animals were divided randomly into normal control, AA, SHR0302 (0.3,1.0, 3.0 mg/kg) and MTX. The effects of SHR0302 on AA rats by evaluating arthritis index, arthritis global assessment and paw swelling degree, histopathology of joint and spleen. We examined the proliferation of T, B and FLS. Th17, Treg, total B and memory B cell proportion was measured by flow cytometry. Cytokines TNF-alpha, IL-1 beta, IL-10, IL-17 and antibody IgG1, IgG2a levels in serum were measured by Elisa. The expression of p-JAK1 and p-STAT3 was measured by western blot. Results: SHR0302 suppressed the severity of AA rats by attenuating the arthritis index, arthritis global assessment and paw swelling degree, and alleviated histopathology of spleen and joint of AA rats. SHR0302 can inhibit the proliferation of T, B and FLS, and down-regulated cytokines TNF-alpha, IL -1 beta, IL-17 and antibody IgG1, IgG2a levels, and suppressed the proportion of Th17 and total B, and inhibited JAK1-STAT3 phosphorylation. There was no significant effect on Treg function and memory B cell proportion. Conclusion: SHR0302 may attenuate the severity of AA rats, partially through reducing Th17 function and total B cell proportion by inhibiting JAK1-STAT3 phosphorylation. (C) 2015 Societe francaise de rhumatologie. Published by Elsevier Masson SAS. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available