Prostaglandin F2 alpha upregulates intercellular adhesion molecule-1 expression in human gingival fibroblasts.
Prostaglandin F2 alpha (PGF2 alpha) is a bioactive lipid mediator, which has been suggested to be involved in the pathogenesis of periodontal disease. However, the roles of PGF2 alpha in the disease are not well understood. In the present study, we investigated the effect of PGF2 alpha on intercellular adhesion molecule-1 (ICAM-1) expression in human gingival fibroblasts (HGF) and the effect of PGF2 alpha on ICAM-1 expression elicited by proinflammatory cytokines, interferon-gamma (IFN-gamma) and tumour necrosis factor alpha (TNF alpha) in the cells. PGF2 alpha-stimulated HGF expressed ICAM-1 expression in a time- and dose-dependent manner. IFN-gamma-elicited ICAM-1 expression was synergistically increased by PGF2 alpha, whereas TNF alpha- induced ICAM-1 expression was slightly inhibited by PGF2 alpha. Fluprostenol, a selective FP receptor agonist, could mimic PGF2 alpha-induced effect on ICAM-1 expression. Furthermore, signal transduction for the regulation of ICAM-1 by PGF2 alpha was investigated using N-(6-aminohexyl)-5-chloro-1-naphthalenesulphonamide (W-7), a calcium calmodulin antagonist, and 1-(5-isoquinolinylsulphonyl)-2-methylpiperazine (H-7), an inhibitor of protein kinase C (PKC). W-7 and H-7, remarkably, suppressed PGF2 alpha-induced ICAM-1 expression and synergistic increase of ICAM-1 expression by combination of PGF2 alpha and IFN-gamma, while IFN-gamma-elicited ICAM-1 expression was only partially inhibited by W-7 and H-7. From these data, we suggest that PGF2 alpha upregulates ICAM-1 expression in HGF and synergistically enhances IFN-gamma- induced ICAM-1 expression through FP receptor by calcium calmodulin-dependent and PKC-dependent pathways. PGF2 alpha may be involved in the pathology of periodontal disease by upregulating ICAM-1 expression in HGF.[1]References
- Prostaglandin F2 alpha upregulates intercellular adhesion molecule-1 expression in human gingival fibroblasts. Noguchi, K., Iwasaki, K., Ishikawa, I. J. Periodont. Res. (1999) [Pubmed]
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