PMID- 10190904
OWN - NLM
STAT- MEDLINE
DCOM- 19990506
LR  - 20190508
IS  - 0022-1007 (Print)
IS  - 0022-1007 (Linking)
VI  - 189
IP  - 7
DP  - 1999 Apr 5
TI  - Defective interleukin (IL)-18-mediated natural killer and T helper cell type 1
      responses in IL-1 receptor-associated kinase (IRAK)-deficient mice.
PG  - 1129-38
AB  - 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)-kappaB. 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-kappaB activation were found in
      IRAK-deficient Th1 cells, resulting in a dramatic decrease in interferon
      (IFN)-gamma mRNA expression. In vivo Th1 response to Propionibacterium acnes and 
      lipopolysaccharide in IFN-gamma production and induction of NK cytotoxicity by
      IL-18 were severely impaired in IRAK-deficient mice. IFN-gamma 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.
FAU - Kanakaraj, P
AU  - Kanakaraj P
AD  - R.W. Johnson Pharmaceutical Research Institute, San Diego, California 92121, USA.
FAU - Ngo, K
AU  - Ngo K
FAU - Wu, Y
AU  - Wu Y
FAU - Angulo, A
AU  - Angulo A
FAU - Ghazal, P
AU  - Ghazal P
FAU - Harris, C A
AU  - Harris CA
FAU - Siekierka, J J
AU  - Siekierka JJ
FAU - Peterson, P A
AU  - Peterson PA
FAU - Fung-Leung, W P
AU  - Fung-Leung WP
LA  - eng
GR  - AI30627/AI/NIAID NIH HHS/United States
GR  - CA66167/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Exp Med
JT  - The Journal of experimental medicine
JID - 2985109R
RN  - 0 (Il18r1 protein, mouse)
RN  - 0 (Interleukin-18)
RN  - 0 (Interleukin-18 Receptor alpha Subunit)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (NF-kappa B)
RN  - 0 (Receptors, Interleukin)
RN  - 0 (Receptors, Interleukin-18)
RN  - 207137-56-2 (Interleukin-4)
RN  - 82115-62-6 (Interferon-gamma)
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.11.1 (Interleukin-1 Receptor-Associated Kinases)
RN  - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinases)
RN  - EC 2.7.11.24 (JNK Mitogen-Activated Protein Kinases)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
SB  - IM
SB  - X
MH  - Animals
MH  - Calcium-Calmodulin-Dependent Protein Kinases/biosynthesis/genetics
MH  - Cell Differentiation/drug effects
MH  - Cell Division/drug effects
MH  - Chimera
MH  - Crosses, Genetic
MH  - Cytomegalovirus Infections/immunology
MH  - Cytotoxicity, Immunologic/drug effects
MH  - Depression, Chemical
MH  - Enzyme Activation/drug effects
MH  - Enzyme Induction/drug effects
MH  - Female
MH  - Gene Expression Regulation/drug effects
MH  - Interferon-gamma/biosynthesis/genetics
MH  - Interleukin-1 Receptor-Associated Kinases
MH  - Interleukin-18/*pharmacology
MH  - Interleukin-18 Receptor alpha Subunit
MH  - Interleukin-4/biosynthesis/genetics
MH  - JNK Mitogen-Activated Protein Kinases
MH  - Killer Cells, Natural/*immunology
MH  - Lipopolysaccharides/immunology
MH  - Lymphocyte Activation/drug effects
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - *Mitogen-Activated Protein Kinases
MH  - NF-kappa B/metabolism
MH  - Propionibacterium acnes/immunology
MH  - Protein Kinases/*deficiency/genetics/physiology
MH  - Receptors, Interleukin/physiology
MH  - Receptors, Interleukin-18
MH  - Signal Transduction/*physiology
MH  - Th1 Cells/cytology/*immunology
MH  - Th2 Cells/cytology/immunology
PMC - PMC2193007
EDAT- 1999/04/06 00:00
MHDA- 1999/04/06 00:01
CRDT- 1999/04/06 00:00
PHST- 1999/04/06 00:00 [pubmed]
PHST- 1999/04/06 00:01 [medline]
PHST- 1999/04/06 00:00 [entrez]
AID - 10.1084/jem.189.7.1129 [doi]
PST - ppublish
SO  - J Exp Med. 1999 Apr 5;189(7):1129-38. doi: 10.1084/jem.189.7.1129.