Astilbin inhibits contact hypersensitivity through negative cytokine regulation distinct from cyclosporin A
Astilbin inhibits contact hypersensitivity through negative cytokine regulation distinct from cyclosporin A
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DOI：
10.1016/j.jaci.2005.08.032
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发表时间：
2005-12-01
影响因子：
14.2
通讯作者：
Xu, Q
中科院分区：
文献类型：
--
作者：
Fei, MJ;Wu, XF;Xu, Q
背景：IL-10被认为是炎症性疾病（包括接触性皮炎）的负调节因子。然而，目前只有少数药物能诱导内源性IL-10的产生。目的：与环孢素A相比，落新妇苷可能通过负性细胞因子调节而发挥免疫抑制作用。方法：用苦酰氯诱发小鼠接触性超敏反应。分离淋巴结细胞用于过继转移和细胞因子测定。结果：落新妇苷在诱导期给药时显着抑制接触性超敏反应，但在致敏期不抑制，而环孢菌素A则抑制这两个阶段。给落新妇苷的供体小鼠的淋巴结细胞不能过继转移超敏反应。落新妇苷在体内可显著诱导淋巴结细胞中IL-10在较早的时间表达，并在较晚的时间降低TNF-α和IFN-γ的表达。此外，IL-10的体内中和作用显著削弱落新妇苷对接触性超敏反应的作用。在苦基氯体内致敏和三硝基苯磺酸体外激发的分离淋巴细胞中，落新妇苷不影响细胞增殖，但以浓度依赖性方式调节上述细胞因子谱，并显着增强细胞因子信号抑制因子1和3的表达。另一方面，环孢菌素A强烈抑制促炎细胞因子的产生，但既不影响IL-10也不影响下游抑制因子1和3的表达。结论：落新妇苷通过一种独特的机制，涉及通过刺激IL-10，这是不同的免疫抑制剂环孢菌素A的负性细胞因子的调节，从而减轻接触性过敏。
Background: IL-10 is known as a negative regulator for inflammatory diseases, including contact dermatitis. However, only a few drug candidates are reported to induce endogenous IL-10.Objective: We sought to elucidate a new mechanism underlying the immunosuppressive properties of astilbin through negative cytokine regulation in comparison with the effective pattern with cyclosporin A. Methods: Contact hypersensitivity was induced in mice with picryl chloride. Lymph node cells were isolated for adoptive transfer and cytokine assays.Results: Astilbin significantly inhibited contact hypersensitivity when given in the elicitation phase but not in the sensitization phase, whereas cyclosporin A inhibited both phases. Lymph node cells from donor mice administered astilbin failed to adoptively transfer the hypersensitivity. Astilbin in vivo remarkably induced IL-10 expression in lymph node cells at an earlier time and decreased TNF-alpha and IFN-gamma expression at a later time. Furthermore, the in vivo neutralization of IL-10 significantly impaired the effect of astilbin on contact hypersensitivity. In the isolated lymphocytes sensitized with picryl chloride in vivo and challenged with trinitrobenzenesulfonic acid in vitro, astilbin did not affect the cell proliferation but modulated the above cytokine profiles as its in vivo effect in a concentration-dependent manner and furthermore significantly enhanced the expressions of suppressor of cytokine signaling 1 and 3. On the other band, cyclosporin A strongly inhibited proinflammatory cytokine production but influenced neither IL-10 nor downstream suppressor of cytokine signaling 1 and 3 expression.Conclusion: Astilbin alleviates contact hypersensitivity through a unique mechanism involving a negative cytokine regulation through stimulating IL-10, which is distinct from the immunosuppressant cyclosporin A.