Document Type
Article
Publication Date
4-5-1999
Journal / Book Title
Journal of Experimental Medicine
Abstract
Interleukin (IL)-18 is functionally similar to IL-12 in mediating T helper cell type 1 (Th1) response and natural killer (NK) cell activity but is related to IL-1 in protein structure and signaling, including recruitment of IL-1 receptor-associated kinase (IRAK) to the receptor and activation of c-Jun NH2-terminal kinase (JNK) and nuclear factor (NF)-κB. The role of IRAK in IL-18-induced responses was studied in IRAK-deficient mice. Significant defects in JNK induction and partial impairment in NF-κB activation were found in IRAK-deficient Th1 cells, resulting in a dramatic decrease in interferon (IFN)-γ mRNA expression. In vivo Th1 response to Propionibacterium aches and lipopolysaccharide in IFN-γ production and induction of NK cytotoxicity by IL-18 were severely impaired in IRAK- deficient mice. IFN-γ production by activated NK cells in an acute murine cytomegalovirus infection was significantly reduced despite normal induction of NK cytotoxicity. These results demonstrate that IRAK plays an important role in IL-18-induced signaling and function.
DOI
10.1084/jem.189.7.1129
Montclair State University Digital Commons Citation
Kanakaraj, Palanisamy; Ngo, Karen; Wu, Ying; Angulo, Ana; Ghazal, Peter; Harris, Crafford A.; Siekierka, John; Peterson, Per A.; and Fung-Leung, Wai Ping, "Defective Interleukin (IL)-18-Mediated Natural Killer and T Helper Cell Type 1 Responses in IL-1 Receptor-Associated Kinase (IRAK)-Deficient Mice" (1999). Department of Chemistry and Biochemistry Faculty Scholarship and Creative Works. 164.
https://digitalcommons.montclair.edu/chem-biochem-facpubs/164
Rights
This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).