REGULATION OF PROSTAGLANDIN G H SYNTHASE-2 EXPRESSION BY INTERLEUKIN-1 IN HUMAN OSTEOBLAST-LIKE CELLS/

Interleukin-1 (IL-1) is an important factor in bone metabolism, and it s 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 expresse d, 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 prim ary human osteoblastic (HOB) cells, IL-1 induced PGHS-2 mRNA expressio n in MG-63 cells nil hin 1 h, and expression was maintained for 24 In. 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 (P GE2) paralleled induction of PGHS-2 mRNA levels, IL-1 similarly induce d PGHS-2 mRNA expression and PGE2 production in HOBIT and BOB cells. A mong other potential agonists, phorbol myristate acetate (PMA) was a p otent induces of PGHS-2 expression, while forskolin (FSK), serum, and prostaglandins had little effect. Cycloheximide enhanced effects of bo th IL-1 and PMA, suggesting that de novo protein synthesis is not requ ired for induction of PGHS-2 Twenty-four hours of PMA pretreatment blo cked the induction of PGHS-2 by PMA but not by IL-1, suggesting that I L-1 induction of PGHS-2 mRNA is not dependent on the protein kinase C pathway. Although FSK alone had little effect, it enhanced induction o f 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 poten t inducer of PGHS-2 expression and PGE2 production in human osteosarco ma cells as well as in osteoblastic cells derived from normal human bo ne.