Takezako Naoki, Hayakawa Morisada, Hayakawa Hiroko, Aoki Shinsuke, Yanagisawa Ken, Endo Hitoshi, Tominaga Shin-ichi
Department of Biochemistry, Jichi Medical School, 3311-1 Yakushiji, Minamikawachi-machi, Kawachi-gun, Tochigi 329-0498, Japan.
Biochem Biophys Res Commun. 2006 Mar 10;341(2):425-32. doi: 10.1016/j.bbrc.2005.12.206. Epub 2006 Jan 11.
LPS induces the production of inflammatory cytokines via the stimulation of Toll-like receptors. In this study, we demonstrated that a soluble secreted form of the ST2 gene product (ST2), a member of the interleukin-1 receptor family, suppressed the production of IL-6 in an LPS-stimulated human monocytic leukemia cell line, THP-1. Immunofluorescence confocal microscopy revealed the binding of ST2 to the surface of the THP-1 cells, in which ST2 led to decreased binding of nuclear factor-kappaB to the IL-6 promoter. Furthermore, the degradation of IkappaB in the cytoplasm after LPS stimulation was reduced by pretreatment with ST2. These results demonstrated that ST2 negatively regulates LPS-induced IL-6 production via the inhibition of IkappaB degradation in THP-1 cells.
脂多糖通过刺激Toll样受体诱导炎性细胞因子的产生。在本研究中，我们证明白细胞介素-1受体家族成员ST2基因产物（ST2）的可溶性分泌形式，可抑制脂多糖刺激的人单核细胞白血病细胞系THP-1中IL-6的产生。免疫荧光共聚焦显微镜显示ST2与THP-1细胞表面结合，其中ST2导致核因子-κB与IL-6启动子的结合减少。此外，用ST2预处理可减少脂多糖刺激后细胞质中IκB的降解。这些结果表明，ST2通过抑制THP-1细胞中IκB的降解来负向调节脂多糖诱导的IL-6产生。
