title: Regulation of prostaglandin G/H synthase-2 expression by interleukin-1 in human osteoblast-like cells.
abstract: Interleukin-1 (IL-1) is an important factor in bone metabolism, and its actions may be mediated in part via prostaglandins. Prostaglandin G/H synthase (PGHS), a critical enzyme in the synthesis of prostaglandins, has two isoforms, PGHS-1, which is generally constitutively expressed, and PGHS-2, which is inducible. This study examines the effects of IL-1 on PGHS-2 mRNA expression in human osteosarcoma MG-63 cells, the human osteoblast-like initial transfectant (HOBIT) cell line, and primary human osteoblastic (HOB) cells. IL-1 induced PGHS-2 mRNA expression in MG-63 cells within 1 h, and expression was maintained for 24 h. There was a dose-related increase in PGHS-2 mRNA levels with 1-100 ng/ml of IL-1. Induction of PGHS-2 protein and media prostaglandin E2 (PGE2) paralleled induction of PGHS-2 mRNA levels. IL-1 similarly induced PGHS-2 mRNA expression and PGE2 production in HOBIT and HOB cells. Among other potential agonists, phorbol myristate acetate (PMA) was a potent inducer of PGHS-2 expression, while forskolin (FSK), serum, and prostaglandins had little effect. Cycloheximide enhanced effects of both IL-1 and PMA, suggesting that de novo protein synthesis is not required for induction of PGHS-2. Twenty-four hours of PMA pretreatment blocked the induction of PGHS-2 by PMA but not by IL-1, suggesting that IL-1 induction of PGHS-2 mRNA is not dependent on the protein kinase C pathway. Although FSK alone had little effect, it enhanced induction of PGHS-2 mRNA by IL-1. PGHS-1 was constitutively expressed and showed little change with treatment. In summary, we show that IL-1 is a potent inducer of PGHS-2 expression and PGE2 production in human osteosarcoma cells as well as in osteoblastic cells derived from normal human bone.
authors.affiliation: Department of Medicine, University of Connecticut Health Center, Farmington, USA.
authors.forename: Y K
authors.initials: YK
authors.lastname: Min
authors.forename: Y
authors.initials: Y
authors.lastname: Rao
authors.forename: Y
authors.initials: Y
authors.lastname: Okada
authors.forename: L G
authors.initials: LG
authors.lastname: Raisz
authors.forename: C C
authors.initials: CC
authors.lastname: Pilbeam
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D002461:Cell Line, Transformed; D005576:Colforsin / Q000494:pharmacology; D003513:Cycloheximide; D051546:Cyclooxygenase 2; D015232:Dinoprostone / Q000032:analysis; D004305:Dose-Response Relationship, Drug; D004790:Enzyme Induction / Q000187:drug effects; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D007527:Isoenzymes / Q000096:biosynthesis* / Q000235:genetics; D008565:Membrane Proteins; D010006:Osteoblasts / Q000187:drug effects* / Q000201:enzymology; D012516:Osteosarcoma; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis* / Q000235:genetics; D011453:Prostaglandins / Q000494:pharmacology; D011500:Protein Synthesis Inhibitors; D012333:RNA, Messenger / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014162:Transfection; D014407:Tumor Cells, Cultured
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D007375:Interleukin-1; D007527:Isoenzymes; D008565:Membrane Proteins; D011453:Prostaglandins; D011500:Protein Synthesis Inhibitors; D012333:RNA, Messenger; D005576:Colforsin; D003513:Cycloheximide; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone; D013755:Tetradecanoylphorbol Acetate