Central role of IL-6 receptor signal-transducing chain gp130 in activation of L-selectin adhesion by fever-range thermal stress
Central role of IL-6 receptor signal-transducing chain gp130 in activation of L-selectin adhesion by fever-range thermal stress
复制标题
DOI：
10.1016/s1074-7613(03)00358-3
复制
发表时间：
2004-01-01
期刊：
影响因子：
32.4
通讯作者：
Evans, SS
中科院分区：
文献类型：
--
作者：
Chen, Q;Wang, WC;Evans, SS
发热反应的生理益处尚不清楚。本研究表明，发热范围的热应激通过白细胞介素-6 （IL-6）依赖的信号传导机制增强了l -选择素淋巴细胞归巢受体的功能。体外和体内对l-选择素粘附的热刺激是通过IL-6和IL-6受体α (sil - 6rα)结合亚基的可溶性形式参与gp130信号转导链介导的。il -6缺失小鼠的粘附热控制是通过il -6相关细胞因子（即抑癌素M [OSM]、白血病抑制因子[LIF]和IL-11）介导的gp130依赖性代偿机制来维持的。联合生化和药理抑制剂（PD98059, U0126, SB203580, SP600125）方法定位于IL-6/ sil - 6rα信号通路上游的MEK1/ERK1-2，而不是p38 MAPK或JNK，这些信号通路位于l -选择素/细胞骨架相互作用和l -选择素亲和力激活的上游。这些结果强调了gp130相关的IL-6/sIL-6Ralpha转信号在发热炎症反应中放大淋巴细胞运输中的作用。
The physiological benefit of the febrile response is poorly understood. Here we show that fever-range thermal stress enhances the function of the L-selectin lymphocyte homing receptor through an interleukin-6 (IL-6)-dependent signaling mechanism. Thermal stimulation of L-selectin adhesion in vitro and in vivo is mediated by engagement of the gp130 signal-transducing chain by IL-6 and a soluble form of the IL-6 receptor-alpha (sIL-6Ralpha) binding subunit. Thermal control of adhesion is maintained in IL-6-deficient mice through a gp130-dependent compensatory mechanism mediated by IL-6-related cytokines (i.e., oncostatin M [OSM], leukemia inhibitory factor [LIF], and IL-11). Combined biochemical and pharmacological inhibitor (PD98059, U0126, SB203580, SP600125) approaches positioned MEK1/ERK1-2, but not p38 MAPK or JNK in the IL-6/sIL-6Ralpha signaling pathway upstream of activation of L-selectin/cytoskeletal interactions and L-selectin avidity/affinity. These results highlight a role for gp130-linked IL-6/sIL-6Ralpha transsignaling in amplifying lymphocyte trafficking during febrile inflammatory responses.