PMID- 9266843 OWN - NLM STAT- MEDLINE DCOM- 19970908 LR - 20171116 IS - 0006-291X (Print) IS - 0006-291X (Linking) VI - 237 IP - 1 DP - 1997 Aug 8 TI - Interleukin-18 induces activation and association of p56(lck) and MAPK in a murine TH1 clone. PG - 126-30 AB - Interleukin-18 (IL-18) was identified as an inducer of interferon-gamma (IFN-gamma) production by stimulated T cells. In this study, we used an ovalbumin-responsive murine Th1 clone (OVA#4), in which DNA synthesis was reportedly enhanced after IL-18 treatment in the presence of a non-mitogenic TCR/CD3 stimulus, to examine signal transduction pathways. In the presence of the stimulus, IL-18 induced the appearance of tyrosine-phosphorylated proteins and herbimycin A inhibited DNA synthesis. It is suggested that protein tyrosine kinase (PTK) mediated signaling is induced by IL-18. Specifically, IL-18 induced phosphorylation of phosphorylates p56(lck) (LCK) and mitogen-activated protein kinase (MAPK). IL-18 alone induced the kinase activities of both LCK and MAPK, and the activities were increased by the TCR/CD3 stimulus. Simultaneously, IL-18 induced the association of LCK with MAPK and this was also increased by the TCR/CD3 stimulus. The activation of the LCK-MAPK pathway correlated with enhanced DNA synthesis in OVA#4 cells. These results suggest that the LCK-MAPK pathway is involved in IL-18 signaling and that IL-18 may play an important role in modification of TCR/CD3-mediated response. FAU - Tsuji-Takayama, K AU - Tsuji-Takayama K AD - Fujisaki Institute, Hayashibara Biochemical Laboratories, Inc., Okayama, Japan. fujih@po.harenet.or.jp FAU - Matsumoto, S AU - Matsumoto S FAU - Koide, K AU - Koide K FAU - Takeuchi, M AU - Takeuchi M FAU - Ikeda, M AU - Ikeda M FAU - Ohta, T AU - Ohta T FAU - Kurimoto, M AU - Kurimoto M LA - eng PT - Journal Article PL - United States TA - Biochem Biophys Res Commun JT - Biochemical and biophysical research communications JID - 0372516 RN - 0 (Antibodies, Monoclonal) RN - 0 (Benzoquinones) RN - 0 (CD3 Complex) RN - 0 (Cytokines) RN - 0 (Enzyme Inhibitors) RN - 0 (Interleukin-18) RN - 0 (Lactams, Macrocyclic) RN - 0 (Quinones) RN - 1W306TDA6S (Rifabutin) RN - 70563-58-5 (herbimycin) RN - EC 2.7.10.1 (Protein-Tyrosine Kinases) RN - EC 2.7.10.2 (Lymphocyte Specific Protein Tyrosine Kinase p56(lck)) RN - EC 2.7.10.2 (src-Family Kinases) RN - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinases) SB - IM MH - Animals MH - Antibodies, Monoclonal/pharmacology MH - Benzoquinones MH - CD3 Complex/immunology/physiology MH - Calcium-Calmodulin-Dependent Protein Kinases/*metabolism MH - Clone Cells MH - Cytokines/*pharmacology MH - DNA Replication/drug effects MH - Enzyme Activation MH - Enzyme Inhibitors/pharmacology MH - Interleukin-18 MH - Kinetics MH - Lactams, Macrocyclic MH - Lymphocyte Activation MH - Lymphocyte Specific Protein Tyrosine Kinase p56(lck) MH - Mice MH - Protein-Tyrosine Kinases/antagonists & inhibitors/metabolism MH - Quinones/pharmacology MH - Rifabutin/analogs & derivatives MH - Th1 Cells/drug effects/immunology/*physiology MH - Time Factors MH - src-Family Kinases/*metabolism EDAT- 1997/08/08 00:00 MHDA- 1997/08/08 00:01 CRDT- 1997/08/08 00:00 PHST- 1997/08/08 00:00 [pubmed] PHST- 1997/08/08 00:01 [medline] PHST- 1997/08/08 00:00 [entrez] AID - S0006-291X(97)97099-6 [pii] AID - 10.1006/bbrc.1997.7099 [doi] PST - ppublish SO - Biochem Biophys Res Commun. 1997 Aug 8;237(1):126-30. doi: 10.1006/bbrc.1997.7099.