PMID- 10486154 OWN - NLM STAT- MEDLINE DCOM- 19991021 LR - 20171116 IS - 0008-8749 (Print) IS - 0008-8749 (Linking) VI - 196 IP - 1 DP - 1999 Aug 25 TI - Interleukin-18 induces interferon-gamma production through NF-kappaB and NFAT activation in murine T helper type 1 cells. PG - 41-50 AB - Interleukin-18 (IL-18) combined with anti-CD3 monoclonal antibody (mAb) induced interferon-gamma (IFN-gamma) production by T helper type 1 (Th1) cells. Neither IL-18 nor anti-CD3 mAb alone induced production of IFN-gamma. Although treatment with IL-18 alone induced full activation of NF-kappaB in Th1 cells, it was not sufficient for the production of IFN-gamma. To examine the importance of NF-kappaB activation in IFN-gamma production, we established Th1 cells which expressed a transdominant IkappaBalpha mutant. In these cells, activation of NF-kappaB and production of IFN-gamma by IL-18 were suppressed. On the other hand, we examined the T cell receptor (TCR)/CD3-mediated signaling pathway. FK506, an inhibitor of NFAT activation, inhibited IFN-gamma production by IL-18 without any effect on the NF-kappaB activation. We conclude that dual signaling consisting of IL-18-induced NF-kappaB activation and TCR/CD3-mediated NFAT activation is crucial for IFN-gamma production by IL-18 in murine Th1 cells. CI - Copyright 1999 Academic Press. FAU - Tsuji-Takayama, K AU - Tsuji-Takayama K AD - Fujisaki Institute, Hayashibara Biochemical Laboratories, Inc., 675-1 Fujisaki, Okayama, 702-8006, Japan. FAU - Aizawa, Y AU - Aizawa Y FAU - Okamoto, I AU - Okamoto I FAU - Kojima, H AU - Kojima H FAU - Koide, K AU - Koide K FAU - Takeuchi, M AU - Takeuchi M FAU - Ikegami, H AU - Ikegami H FAU - Ohta, T AU - Ohta T FAU - Kurimoto, M AU - Kurimoto M LA - eng PT - Journal Article PL - Netherlands TA - Cell Immunol JT - Cellular immunology JID - 1246405 RN - 0 (Antibodies, Monoclonal) RN - 0 (CD3 Complex) RN - 0 (DNA-Binding Proteins) RN - 0 (I-kappa B Proteins) RN - 0 (Interleukin-18) RN - 0 (Isoenzymes) RN - 0 (NF-kappa B) RN - 0 (NFATC Transcription Factors) RN - 0 (NFKBIA protein, human) RN - 0 (Nfkbia protein, mouse) RN - 0 (Nuclear Proteins) RN - 0 (Transcription Factors) RN - 139874-52-5 (NF-KappaB Inhibitor alpha) RN - 82115-62-6 (Interferon-gamma) RN - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinases) RN - EC 3.1.4.- (Type C Phospholipases) RN - EC 3.1.4.3 (Phospholipase C gamma) RN - WM0HAQ4WNM (Tacrolimus) SB - IM MH - Animals MH - Antibodies, Monoclonal MH - CD3 Complex/immunology MH - Calcium-Calmodulin-Dependent Protein Kinases/metabolism MH - Cells, Cultured MH - DNA-Binding Proteins/genetics/*metabolism MH - Humans MH - *I-kappa B Proteins MH - Interferon-gamma/*biosynthesis MH - Interleukin-18/*physiology MH - Isoenzymes/metabolism MH - Mice MH - NF-KappaB Inhibitor alpha MH - NF-kappa B/*metabolism MH - NFATC Transcription Factors MH - *Nuclear Proteins MH - Phospholipase C gamma MH - Phosphorylation MH - Signal Transduction MH - Tacrolimus/metabolism/pharmacology MH - Th1 Cells/drug effects/*metabolism MH - Transcription Factors/*metabolism MH - Transformation, Genetic MH - Type C Phospholipases/metabolism EDAT- 1999/09/16 00:00 MHDA- 1999/09/16 00:01 CRDT- 1999/09/16 00:00 PHST- 1999/09/16 00:00 [pubmed] PHST- 1999/09/16 00:01 [medline] PHST- 1999/09/16 00:00 [entrez] AID - S0008-8749(99)91542-3 [pii] AID - 10.1006/cimm.1999.1542 [doi] PST - ppublish SO - Cell Immunol. 1999 Aug 25;196(1):41-50. doi: 10.1006/cimm.1999.1542.