IL-18; a cytokine translates a stress into medical science.
IL-18; a cytokine translates a stress into medical science.
复制标题
DOI：
10.2152/jmi.52.236
复制
发表时间：
2005-11
期刊：
影响因子：
--
通讯作者：
A. Sekiyama;H. Ueda;S. Kashiwamura;K. Nishida;Kaori Kawai;S. Teshima-kondo;K. Rokutan;H. Okamura
中科院分区：
文献类型：
--
作者：
A. Sekiyama;H. Ueda;S. Kashiwamura;K. Nishida;Kaori Kawai;S. Teshima-kondo;K. Rokutan;H. Okamura
据报道，心理/身体压力会加剧自身免疫性和炎症性疾病。为了阐明非炎性应激破坏宿主防御的机制，研究了小鼠对制动应激的反应，重点是多功能细胞因子白细胞介素-18（IL-18）的作用。在肾上腺皮质中，应激通过ACTH和超氧化物介导的半胱天冬酶-1活化途径诱导IL-18前体蛋白（pro-IL-18），导致pro-IL-18转化为成熟形式，释放到血浆中。caspase-1、活性氧和P38 MAPK的抑制剂阻止了应激诱导的血浆IL-18的积累。这些抑制剂还阻断应激诱导的IL-6表达。这与在应激-IL-18缺陷小鼠中未诱导IL-6的观察结果一起表明，应激诱导的IL-6依赖于IL-18。在应激生物体中，IL-18可影响病理和生理过程。控制半胱天冬酶-1活化途径以抑制IL-18水平可以提供针对应激相关的宿主防御破坏的预防手段。
Psychological/physical stresses have been reported to exacerbate auto-immune and inflammatory diseases. To clarify a mechanism by which non-inflammatory stresses disrupt host defenses, responses to immobilization stress in mice were investigated, focusing on the role of a multifunctional cytokine, interleukin-18 (IL-18). In the adrenal cortex, the stress induced IL-18 precursor proteins (pro-IL-18) via ACTH and a superoxide-mediated caspase-1 activation pathway, resulting in conversion of pro-IL-18 to the mature form which was released into plasma. Inhibitors of caspase-1, reactive oxygen species and P38 MAPK prevented stress-induced accumulation of plasma IL-18. These inhibitors also blocked stress-induced IL-6 expression. This, together with the observation that IL-6 was not induced in stressed-IL-18 deficient mice, showed that IL-6 induction by stress is dependent on IL-18. In stressed organisms, IL-18 may influence pathological and physiological processes. Controlling the caspase-1 activating pathway to suppress IL-18 levels may provide preventative means against stress-related disruption of host defenses.