Polentarutti Nadia, Rol Giselle Penton, Muzio Marta, Bosisio Daniela, Camnasio Marco, Riva Federica, Zoja Carla, Benigni Ariela, Tomasoni Susanna, Vecchi Annunciata, Garlanda Cecilia, Mantovani Alberto
Dept. Immunology and Cell Biology, Mario Negri Institute for Pharmacological Research, Milan, 20157, Italy.
Eur Cytokine Netw. 2003 Oct-Dec;14(4):211-8.
TIR8, also known as single Ig IL-1R-related molecule (SIGIRR), is a member of the IL-1 receptor family. The present study was designed to investigate the expression and function of TIR8. TIR8 was mainly expressed in mouse and human epithelial tissues such as kidney, lung and gut. Resting and activated T and B lymphocytes and monocytes-macrophages expressed little or no TIR8, with the exception of the mouse GG2EE macrophage line. In the kidney, the organ with highest mRNA levels, TIR8 expression was confined to epithelial cells and, in situ, to tubular epithelium. A variety of signals failed to regulate TIR8 expression, but LPS reduced TIR8 mRNA transcripts. An NF-kB driven reporter system was used to investigate the function of TIR8. TIR8 did not activate NF-kB expression alone or in concert with IL-1R1. In contrast, TIR8 inhibited signaling from the IL-1R complex. Inhibition required the intracellular portion of TIR8 but the extracellular domain was dispensable for blocking activity. Thus, TIR8 is a unique member of the IL-1R family, with a distinct pattern of epithelial expression, including the kidney and mucosae, and an inhibitory function on IL-1 signaling.
TIR8，也被称为单免疫球蛋白白细胞介素-1受体相关分子（SIGIRR），是白细胞介素-1受体家族的一员。本研究旨在探究TIR8的表达及功能。TIR8主要在小鼠和人类的上皮组织中表达，如肾脏、肺和肠道。静息和活化的T淋巴细胞、B淋巴细胞以及单核细胞-巨噬细胞很少或不表达TIR8，但小鼠GG2EE巨噬细胞系除外。在mRNA水平最高的器官——肾脏中，TIR8的表达局限于上皮细胞，在原位则局限于肾小管上皮。多种信号未能调节TIR8的表达，但脂多糖可减少TIR8的mRNA转录本。使用一种由核因子κB驱动的报告系统来研究TIR8的功能。TIR8单独或与白细胞介素-1受体1共同作用时均不激活核因子κB的表达。相反，TIR8可抑制来自白细胞介素-1受体复合物的信号传导。这种抑制作用需要TIR8的胞内部分，但胞外结构域对于阻断活性而言并非必需。因此，TIR8是白细胞介素-1受体家族的一个独特成员，具有独特的上皮表达模式，包括在肾脏和黏膜中的表达，并且对白细胞介素-1信号传导具有抑制功能。
