Chicken type II collagen induced immune tolerance of mesenteric lymph node lymphocytes by enhancing beta2-adrenergic receptor desensitization in rats with collagen-induced arthritis.
Chicken type II collagen (CCII) is a protein extracted from the cartilage of chicken breast and exhibits intriguing possibilities for the treatment of autoimmune diseases by inducing oral tolerance. In this study, we investigated the effects of CCII on inflammatory and immune responses to the mesenteric lymph node lymphocytes (MLNLs) and the mechanisms by which CCII regulates beta2-adrenergic receptor (beta2-AR) signal transduction in collagen-induced arthritis (CIA) rats. The onset of secondary arthritis in rats appeared around day 14 after injection of CCII emulsion. Remarkable secondary inflammatory response and lymphocytes proliferation were observed in CIA rats. The administration of CCII (10, 20, 40μgkg(-1)day(-1), days 15-22) could significantly reduce synovial hyperplasia, lymphatic follicle hyperplasia, inflammatory cells infiltration of MLNLs in CIA rats. CCII (10, 20, 40μgkg(-1)day(-1), days 15-22) restored the previously decreased level of cAMP of MLNLs of CIA rats. Meanwhile, CCII increased total protein expressions of beta2-AR, GRK2 and decreased that of beta-arrestin1, 2 of MLNLs in CIA rats but had an slight effect on GRK3. CCII further increased plasmatic protein expressions of GRK2, G(α)s and decreased that of beta-arrestin1, 2, beta2-AR, and increased membrane protein expressions of beta2-AR, GRK2, G(α)s and decreased that of beta-arrestin1, 2 of MLNLs in CIA rats. These results demonstrate that the mechanisms of CCII on beta2-AR desensitization and beta2-AR-AC-cAMP transmembrane signal transduction of MLNLs play crucial roles in pathogenesis of this disease.
Zhao
Wei
W
Institute of Clinical Pharmacology, Anhui Medical University, China. zhaoweiroy@126.com
Tong
Tong
T
Wang
Ling
L
Li
Pei-Pei
PP
Chang
Yan
Y
Zhang
Ling-Ling
LL
Wei
Wei
W
D000818:Animals; D001169:Arthritis, Experimental / Q000188:drug therapy* / Q000276:immunology; D002645:Chickens; D024043:Collagen Type II / Q000276:immunology* / Q000302:isolation & purification / Q000627:therapeutic use*; D000242:Cyclic AMP / Q000096:biosynthesis; D007108:Immune Tolerance / Q000187:drug effects* / Q000276:immunology; D008198:Lymph Nodes / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D008214:Lymphocytes / Q000187:drug effects* / Q000276:immunology; D008297:Male; D008643:Mesentery / Q000276:immunology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018343:Receptors, Adrenergic, beta-2 / Q000096:biosynthesis*; D015398:Signal Transduction / Q000187:drug effects; D013583:Synovial Membrane / Q000187:drug effects / Q000276:immunology / Q000473:pathology
D024043:Collagen Type II; D018343:Receptors, Adrenergic, beta-2; D000242:Cyclic AMP