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 induced immune tolerance of mesenteric lymph node lymphocytes by enhancing beta2-adrenergic receptor desensitization in rats with collagen-induced arthritis.
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DOI：
10.1016/j.intimp.2010.09.018
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发表时间：
2011
影响因子：
5.6
通讯作者：
Wei Zhao;Tong Tong-Tong;Ling Wang;Peipei Li;Yan Chang;Lingling Zhang;Wei Wei-Wei
中科院分区：
文献类型：
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作者：
Wei Zhao;Tong Tong-Tong;Ling Wang;Peipei Li;Yan Chang;Lingling Zhang;Wei Wei-Wei
鸡II型胶原蛋白（CCII）是从鸡胸软骨中提取的蛋白质，通过诱导口服耐受来治疗自身免疫性疾病。在这项研究中，我们研究了CCII对肠系膜淋巴结淋巴细胞（MLNLs）的炎症和免疫反应的影响以及CCII调节胶原诱导的关节炎（CIA）大鼠β 2-肾上腺素能受体（β 2-AR）信号转导的机制。大鼠继发性关节炎的发病出现在注射CCII乳剂后14天左右。CIA大鼠出现明显的继发性炎症反应和淋巴细胞增殖。CCII（10、20、40μgkg-1day-1，第15-22天）给药可明显减轻CIA大鼠滑膜增生、淋巴滤泡增生、MLNL炎性细胞浸润。CCII（10、20、40μ g/kg-1day-1，第15-22天）恢复了CIA大鼠MLNLs先前降低的cAMP水平。CCII可增加CIA大鼠MLNLs中β 2-AR、GRK 2的总蛋白表达，降低β-arrestin 1、2的总蛋白表达，但对GRK 3影响不大。CCII进一步增加CIA大鼠MLNLs的GRK 2、Gαs的血浆蛋白表达，降低β-arrestin 1，2、β 2-AR的表达;增加MLNLs的β 2-AR、GRK 2、Gαs的膜蛋白表达，降低β-arrestin 1，2的表达。提示CCII对MLNLs的β 2-AR脱敏及β 2-AR-AC-cAMP跨膜信号转导机制在该病的发病机制中起重要作用。
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−1day−1, days 15–22) could significantly reduce synovial hyperplasia, lymphatic follicle hyperplasia, inflammatory cells infiltration of MLNLs in CIA rats. CCII (10, 20, 40μgkg−1day−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, Gαs and decreased that of beta-arrestin1, 2, beta2-AR, and increased membrane protein expressions of beta2-AR, GRK2, Gαs 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.