Open AccessInterleukin‐1 receptor antagonist intervenes in signaling between different types of synoviocytes in rats with adjuvant arthritis 1
Author(s) -
ZHENG Yongqiu,
WEI Wei,
DAI Min,
ZHU Lei,
JIA Xiaoyi,
WANG Yuan
Publication year - 2006
Publication title -
acta pharmacologica sinica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.514
H-Index - 90
eISSN - 1745-7254
pISSN - 1671-4083
DOI - 10.1111/j.1745-7254.2006.00234.x
Subject(s) - endocrinology , medicine , receptor antagonist , kinase , tumor necrosis factor alpha , mapk/erk pathway , prostaglandin e2 , prostaglandin e , extracellular , chemistry , receptor , microbiology and biotechnology , antagonist , biology , biochemistry
Aim: To investigate the mechanisms of interleukin‐1 receptor antagonist (IL‐1ra) in the treatment of adjuvant arthritis (AA). Methods: AA was induced in rats by treatment with Freund's complete adjuvant (FCA). Rats were given an intracutaneous injection of IL‐1ra (2.5,10,40 mg/kg, 3 times per day) from d 14 to d 21 after immunization. Synoviocyte proliferation and the activity of IL‐1 were determined by using MTT assay. Tumor necrosis factor alpha (TNF‐α) and prostaglandin E 2 (PGE 2 ) concentrations were measured by radioimmunoassay. The ultrastructure of synoviocytes was observed by using a transmission electron microscope. Phosphorylation of c‐Jun N‐terminal kinase (JNK), extracellular regulating kinase (ERK) and p38 kinase were detected by Western blot analysis. Results: IL‐1ra (10 and 40 mg/kg, ic, d 14‐21) modulated the secondary inflammatory reaction (P<0.01), ultrastructure of synoviocytes and mitogen‐activated protein kinase (MAPK) phosphorylation in AA rats. The administration of IL‐1ra (10 and 40 mg/kg, ic, d 14‐21) in AA rats significantly decreased the production of IL‐1, PGE2 and TNF‐α by macrophage‐like synoviocytes (MLS) (P<0.01). IL‐1ra (2.5 mg/kg) also decreased the production of PGE 2 (P<0.01) and TNF‐α (P<0.05) by MLS in AA rats. The increased phosphorylation of MAPK and cell proliferation in fibro‐blast‐like synoviocytes (FLS) stimulated by supernatants of MLS in AA rats was also inhibited by IL‐1ra (10 and 40 mg/kg, ic, d 14‐21). Conclusion: IL‐1ra has anti‐inflammatory effects because it modulates the ultrastructure of synoviocytes, decreases the production of pro‐inflammatory mediators by MLS, and inhibits the phosphorylation of MAPK in FLS.