RRC ID 1481
Author Takami Y, Motoki T, Yamamoto I, Gohda E.
Title Synergistic induction of hepatocyte growth factor in human skin fibroblasts by the inflammatory cytokines interleukin-1 and interferon-gamma.
Journal Biochem. Biophys. Res. Commun.
Abstract Hepatocyte growth factor (HGF) is one of the vital factors for wound healing. HGF expression markedly increases in wounded skin and is mainly localized in dermal fibroblasts. HGF expression level in human dermal fibroblasts in vitro, however, is low and thus may be stimulated by some factors in the process of wound healing. Candidates of the factors are inflammatory cytokines released by polymorphonuclear and mononuclear cells infiltrating the wounded area, but HGF production in human dermal fibroblasts is only slightly induced by interleukin (IL)-1, tumor necrosis factor (TNF)-alpha or interferon (IFN)-gamma. We here report that a combination of IL-1beta and IFN-gamma or a combination of TNF-alpha and IFN-gamma very markedly induced HGF production. The synergistic effect of the former was more marked than that of the latter. Synergistic effects of IL-1beta and IFN-gamma were observed at more than 10 pg/ml and 10 IU/ml, respectively, and were detectable as early as 12 h after addition. Neither IFN-alpha nor IFN-beta was able to replace IFN-gamma. HGF mRNA expression was also synergistically upregulated by IL-1beta and IFN-gamma. IL-1beta plus IFN-gamma-induced synergistic production of HGF was potently inhibited by treatment of cells with the extracellular signal-regulated kinase (ERK) kinase inhibitor PD98059 and the p38 inhibitor SB203580 but not by the c-Jun N-terminal kinase (JNK) inhibitor SP600125. Taken together, our results indicate that a combination of IL-1beta and IFN-gamma synergistically induced HGF production in human dermal fibroblasts and suggest that activation of ERK and p38 but not of JNK is involved in the synergistic effect.
Volume 327(1)
Pages 212-7
Published 2005-2-4
DOI 10.1016/j.bbrc.2004.11.144
PII S0006-291X(04)02754-8
PMID 15629451
MeSH Cells, Cultured Drug Synergism Extracellular Signal-Regulated MAP Kinases / antagonists & inhibitors Extracellular Signal-Regulated MAP Kinases / metabolism Fibroblasts Hepatocyte Growth Factor / biosynthesis* Hepatocyte Growth Factor / genetics Hepatocyte Growth Factor / metabolism Humans Inflammation / metabolism Interferon-gamma / pharmacology* Interleukin-1 / pharmacology* Protein Kinase Inhibitors / pharmacology RNA, Messenger / genetics RNA, Messenger / metabolism Skin / drug effects* Skin / metabolism* Up-Regulation / drug effects* p38 Mitogen-Activated Protein Kinases / antagonists & inhibitors p38 Mitogen-Activated Protein Kinases / metabolism
IF 2.705
Times Cited 17
Human and Animal Cells NB1RGB