Sims J E, Gayle M A, Slack J L, Alderson M R, Bird T A, Giri J G, Colotta F, Re F, Mantovani A, Shanebeck K
Department of Molecular Biology, Immunex Research and Development Corporation, Seattle, WA 98101.
Proc Natl Acad Sci U S A. 1993 Jul 1;90(13):6155-9. doi: 10.1073/pnas.90.13.6155.
Two receptors for the proinflammatory cytokine interleukin 1 (IL-1) have been cloned and characterized biochemically. While it has been well established that the type I (80-kDa) IL-1 receptor can mediate responses to IL-1, the function of the type II (60-kDa) IL-1 receptor has been unknown. In this manuscript we describe experiments designed to ask whether the type II receptor is capable of delivering a biological signal. We have examined two types of experimental situation: responses to IL-1 in cells which express predominantly the type II receptor, and responses to IL-1 which have been suggested previously in the literature to be mediated by type II receptors. In both situations we find that the responses instead are mediated via type I receptors. A blocking antibody against the type II receptor never inhibits, and in fact sometimes enhances, the responses. We conclude that a very small number of type I receptors is sufficient to mediate all of the actions of IL-1 which we have examined here and that the function of the type II receptor may not be to transduce signals.
促炎细胞因子白细胞介素1(IL-1)的两种受体已被克隆并进行了生化特性分析。虽然I型(80 kDa)IL-1受体能够介导对IL-1的反应这一点已经得到充分证实,但II型(60 kDa)IL-1受体的功能却一直未知。在本论文中,我们描述了旨在探究II型受体是否能够传递生物信号的实验。我们研究了两种实验情况:在主要表达II型受体的细胞中对IL-1的反应,以及文献中先前认为由II型受体介导的对IL-1的反应。在这两种情况下,我们发现反应实际上是通过I型受体介导的。针对II型受体的阻断抗体从未抑制,事实上有时还会增强这些反应。我们得出结论,极少数的I型受体就足以介导我们在此研究的IL-1的所有作用,并且II型受体的功能可能不是转导信号。