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Regulation of Prostaglandin G/H Synthase‐2 Expression by Interleukin‐1 in Human Osteoblast‐like Cells
Author(s) -
Min YongKi,
Rao Yue,
Okada Yosuke,
Raisz Lawrence G.,
Pilbeam Carol C.
Publication year - 1998
Publication title -
journal of bone and mineral research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.882
H-Index - 241
eISSN - 1523-4681
pISSN - 0884-0431
DOI - 10.1359/jbmr.1998.13.7.1066
Subject(s) - osteoblast , prostaglandin , prostaglandin e2 , endocrinology , medicine , microbiology and biotechnology , chemistry , biology , biochemistry , in vitro
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 E 2 (PGE 2 ) paralleled induction of PGHS‐2 mRNA levels. IL‐1 similarly induced PGHS‐2 mRNA expression and PGE 2 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 PGE 2 production in human osteosarcoma cells as well as in osteoblastic cells derived from normal human bone.