Defective interleukin (IL)-18-mediated natural killer and T helper cell type 1 responses in IL-1 receptor-associated kinase (IRAK)-deficient mice

Palanisamy Kanakaraj, Karen Ngo, Ying Wu, Ana Angulo, Peter Ghazal, Crafford A. Harris, John J. Siekierka, Per A. Peterson, Wai Ping Fung-Leung

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Pages (from-to)1129-1138
Number of pages10
JournalJournal of Experimental Medicine
Volume189
Issue number7
DOIs
StatePublished - 5 Apr 1999

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Interleukin-1 Receptor-Associated Kinases
Natural Killer T-Cells
Interleukin-18
Interferons
Th1 Cells
JNK Mitogen-Activated Protein Kinases
Natural Killer Cells
Muromegalovirus
Propionibacterium
Cytomegalovirus Infections
Interleukin-12
Interleukin-1
Lipopolysaccharides
Pain
Messenger RNA

Keywords

  • C-Jun NH-terminal kinase
  • Inhibitor of nuclear factor κB
  • Interferon γ
  • Murine cytomegalovirus
  • Nuclear factor κB

Cite this

Kanakaraj, Palanisamy ; Ngo, Karen ; Wu, Ying ; Angulo, Ana ; Ghazal, Peter ; Harris, Crafford A. ; Siekierka, John J. ; Peterson, Per A. ; 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. In: Journal of Experimental Medicine. 1999 ; Vol. 189, No. 7. pp. 1129-1138.
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Defective interleukin (IL)-18-mediated natural killer and T helper cell type 1 responses in IL-1 receptor-associated kinase (IRAK)-deficient mice. / Kanakaraj, Palanisamy; Ngo, Karen; Wu, Ying; Angulo, Ana; Ghazal, Peter; Harris, Crafford A.; Siekierka, John J.; Peterson, Per A.; Fung-Leung, Wai Ping.

In: Journal of Experimental Medicine, Vol. 189, No. 7, 05.04.1999, p. 1129-1138.

Research output: Contribution to journalArticle

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