Requirement for type 2 NO synthase for IL-12 signaling in innate immunity

被引：156

作者：

Diefenbach, A

Schindler, H

Röllinghoff, M

Yokoyama, WM

Bogdan, C

机构：

[1] Univ Erlangen Nurnberg, Inst Klin Mikrobiol Immunol & Hyg, D-91054 Erlangen, Germany

[2] Washington Univ, Sch Med, Howard Hughes Med Inst, Div Rheumatol, St Louis, MO 63110 USA

来源：

SCIENCE | 1999年 / 284卷 / 5416期

关键词：

D O I：

10.1126/science.284.5416.951

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Interleukin-12 (IL-12) and type 2 NO synthase (NOS2) are crucial for defense against bacterial and parasitic pathogens, but their relationship in innate immunity is unknown. in the absence of NOS2 activity, IL-12 was unable to prevent spreading of Leishmania parasites, did not stimulate natural killer (NK) cells for cytotoxicity or interferon-gamma (IFN-gamma) release, and failed to activate Tyk2 kinase and to tyrosine phosphorylate Stat4 (the central signal transducer of IL-12) in NK cells. Activation of Tyk2 in NK cells by IFN-alpha/beta also required NOS2. Thus, NOS2-derived NO is a prerequisite for cytokine signaling and function in innate immunity.

引用

页码：951 / 955

页数：5

共 31 条

[1] INTERLEUKIN-12 (IL-12) INDUCES TYROSINE PHOSPHORYLATION OF JAK2 AND TYK2 - DIFFERENTIAL USE OF JANUS FAMILY TYROSINE KINASES BY IL-2 AND IL-12 [J].