title: Protein kinase C activation by interleukin (IL)-1 limits IL-1-induced IL-6 synthesis in osteoblast-like cells: involvement of phosphatidylcholine-specific phospholipase C.
abstract: We investigated the regulatory mechanism of interleukin-6 (IL-6) synthesis induced by interleukin-1 (IL-1) in osteoblast-like MC3T3-E1 cells. IL-1 stimulated the secretion of IL-6 in a dose-dependent manner in the range between 0.1 and 100 ng/ml. Staurosporine and calphostin C, inhibitors of protein kinase C (PKC), significantly enhanced the IL-1-induced secretion of IL-6. The stimulative effect of IL-1 was markedly amplified in PKC down-regulated MC3T3-E1 cells. IL-1 produced diacylglycerol in MC3T3-E1 cells. IL-1 had little effect on the formation of inositol phosphates and choline. On the contrary, IL-1 significantly stimulated the formation of phosphocholine dose-dependently. D-609, an inhibitor of phosphatidylcholine-specific phospholipase C, suppressed the IL-1-induced diacylglycerol production. The IL-1-induced IL-6 secretion was significantly enhanced by D-609. These results indicate that IL-1 activates PKC via phosphatidylcholine-specific phospholipase C in osteoblast-like cells, and the PKC activation then limits IL-6 synthesis induced by IL-1 itself.
authors.affiliation: Department of Pharmacology, Gifu University School of Medicine, Japan.
authors.forename: O
authors.initials: O
authors.lastname: Kozawa
authors.forename: A
authors.initials: A
authors.lastname: Suzuki
authors.forename: H
authors.initials: H
authors.lastname: Tokuda
authors.forename: T
authors.initials: T
authors.lastname: Kaida
authors.forename: T
authors.initials: T
authors.lastname: Uematsu
mesh_terms: D000818:Animals; D001952:Bridged-Ring Compounds / Q000494:pharmacology; D002460:Cell Line; D002794:Choline / Q000378:metabolism; D004075:Diglycerides / Q000096:biosynthesis; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007295:Inositol Phosphates / Q000096:biosynthesis; D007375:Interleukin-1 / Q000494:pharmacology*; D015850:Interleukin-6 / Q000378:metabolism*; D051379:Mice; D009281:Naphthalenes / Q000494:pharmacology; D009636:Norbornanes; D010006:Osteoblasts / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D019311:Staurosporine / Q000494:pharmacology; D013859:Thiocarbamates; D013871:Thiones / Q000494:pharmacology; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors / Q000502:physiology*
chemical_list: D001952:Bridged-Ring Compounds; D004075:Diglycerides; D004791:Enzyme Inhibitors; D007295:Inositol Phosphates; D007375:Interleukin-1; D015850:Interleukin-6; D009281:Naphthalenes; D009636:Norbornanes; D013859:Thiocarbamates; D013871:Thiones; C046498:tricyclodecane-9-yl-xanthogenate; D011493:Protein Kinase C; D010738:Type C Phospholipases; C105598:phosphatidylcholine-specific phospholipase C; D019311:Staurosporine; C058819:calphostin C; D002794:Choline