Bundoc Virgilio G, Keane-Myers Andrea
Exp Eye Res. 2007 Oct;85(4):575-9. doi: 10.1016/j.exer.2007.07.005. Epub 2007 Jul 14.
IL-10 is a regulatory cytokine known to inhibit allergic and inflammatory events. Mast cells (MC) are effector cells which when stimulated release histamine, chemokines and cytokines that initiate the allergic inflammatory response. Recent studies have shown that IL-10 regulates MC function by affecting cytokine production and expression of FcvarepsilonR1 in in vitro assays. Using IL-10 knockout (IL10KO) mice, we examined the effect of its absence on MC susceptibility to degranulation by the basic secretagogue, Compound 48/80 (C48/80). C48/80 is a receptor mimetic that directly activates G proteins and stimulates vigorous MC degranulation. For these studies we stimulated conjunctival MC with C48/80 and found that conjunctival MC of IL10KO mice exhibit increased degranulation compared with wild type mice. Reconstitution of IL10KO mice by adding rIL-10 24h prior to challenge with C48/80 conferred increased resistance of MC to the degranulatory effects of C48/80. The protective effect therefore appears to be due to the presence of IL-10. This is the first in vivo rodent study which reports a novel role of IL-10 in stabilizing mast cells from degranulation by a secretagogue, by as of yet an unknown mechanism.
白细胞介素-10是一种已知可抑制过敏和炎症反应的调节性细胞因子。肥大细胞(MC)是效应细胞,受到刺激时会释放组胺、趋化因子和细胞因子,从而引发过敏性炎症反应。最近的研究表明,在体外试验中,白细胞介素-10通过影响细胞因子的产生和FcεR1的表达来调节肥大细胞的功能。我们使用白细胞介素-10基因敲除(IL10KO)小鼠,研究了其缺失对肥大细胞对碱性促分泌剂化合物48/80(C48/80)脱颗粒敏感性的影响。C48/80是一种受体模拟物,可直接激活G蛋白并刺激肥大细胞剧烈脱颗粒。在这些研究中,我们用C48/80刺激结膜肥大细胞,发现与野生型小鼠相比,IL10KO小鼠的结膜肥大细胞脱颗粒增加。在使用C48/80攻击前24小时给IL10KO小鼠注射重组白细胞介素-10,可增强肥大细胞对C48/80脱颗粒作用的抵抗力。因此,这种保护作用似乎归因于白细胞介素-10的存在。这是第一项关于啮齿动物的体内研究,报告了白细胞介素-10在通过一种尚未明确的机制稳定肥大细胞使其免受促分泌剂诱导的脱颗粒方面的新作用。