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| Interleukin (IL)-1 receptor-associated kinase (IRAK) requirement for optimal induction of multiple IL-1 signaling pathways and IL-6 production |
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| Author(s): Kanakaraj P, Schafer PH, Cavender DE, Wu Y, Ngo K, Grealish PF, Wadsworth SA, Peterson PA, Siekierka JJ, Harris CA, Fung-Leung WP |
| Source: JOURNAL OF EXPERIMENTAL MEDICINE Volume: 187 Issue: 12 Pages: 2073-2079 Published: JUN 15 1998 |
| Times Cited: 131 References: 37 |
| Abstract: Interleukin (IL)-1 is a proinflammatory cytokine with pleiotropic effects in inflammation. IL-1 binding to its receptor triggers a cascade of signaling events, including activation of the stress-activated mitogen-activated protein (MAP) kinases, c-Jun NH2-terminal kinase (JNK) and p38 MAP kinase, as well as transcription factor nuclear factor kappa B (NF-kappa B). IL-1 signaling results in cellular responses through induction of inflammatory gene products such as IL-6. One of the earliest events in IL-1 signaling is the rapid interaction of IL-1 receptor-associated kinases, IRAK and IRAK-2, with the receptor complex. The relative roles of IRAK and IRAK-2 in IL-1 signaling pathways and subsequent cellular responses have not been previously determined. To evaluate the importance of IRAK in IL-1 signaling, IRAK-deficient mouse fibroblast cells were prepared and studied. Here we report that IL-1-mediated activation of JNK, p38, and NF-kappa B were all reduced in embryonic fibroblasts deficient in IRAK expression. In addition, IL-6 production in response to IL-1 was also dramatically reduced in IRAK-deficient embryonic fibroblasts and in skin fibroblasts prepared from IRAK-deficient mice. Our results demonstrate that IRAK plays an essential proximal role in coordinating multiple IL-1signaling pathways for optimal induction of cellular responses. |
| Document Type: Article |
| Language: English |
| Reprint Address: Fung-Leung, WP (reprint author), RW Johnson Pharmaceut Res Inst, 3535 Gen Atom Court, San Diego, CA 92121 USA |
Addresses:
1. RW Johnson Pharmaceut Res Inst, San Diego, CA 92121 USA
2. RW Johnson Pharmaceut Res Inst, Raritan, NJ 08869 USA |
| Publisher: ROCKEFELLER UNIV PRESS, 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA |
| Subject Category: Immunology; Medicine, Research & Experimental |
| IDS Number: ZV462 |
| ISSN: 0022-1007 |
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