The Regulation of PGE2 Biosynthesis in MG-63 Osteosarcoma Cells by IL-1 and FGF Is Cell Density-Dependent

• Published in: Experimental cell research Vol. 258; no. 2; pp. 409 - 416
• Main Authors: Laulederkind, Stanley J.F., Kirtikara, Kanyawim, Raghow, Rajendra, Ballou, Leslie R.
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 01.08.2000
• Subjects: cell density; cytosolic phospholipase A2; fibroblast growth factor 1; interleukin 1β; osteoblast; osteosarcoma; prostaglandin E2; prostaglandin H synthase; interleukin 1β; cell density; prostaglandin E2; fibroblast growth factor 1; cytosolic phospholipase A2; osteoblast; prostaglandin H synthase; osteosarcoma
• DOI: 10.1006/excr.2000.4961
• ISSN: 0014-4827

We investigated the molecular mechanisms by which treatment of the human osteoblast-like cell line MG-63 with interleukin 1β (IL-1) and/or fibroblast growth factor 1 (FGF-1) elicited prostaglandin biosynthesis. IL-1 induced a 5-fold increase in PGE2 production compared to controls. While treatment with FGF-1 alone did not affect PGE2 biosynthesis, it enhanced the formation of PGE2 by IL-1 by an additional 3- to 5-fold. IL-1-induced PGE2 biosynthesis accompanied increases in steady-state levels of mRNAs encoding cPLA2 (10- to 15-fold) and PGHS-2 (>3-fold) and concomitant increases in cPLA2 protein (>3-fold) and PGHS-2 protein (>1.5-fold). FGF-1 treatment did not affect PGHS-2 gene expression, but enhanced the effect of IL-1 on PGHS-2 expression by an additional 2- to 3-fold. FGF-1 alone enhanced cPLA2 expression (5-fold), and the combined effects of FGF-1 and IL-1 on cPLA2 expression were additive. There was no measurable effect of either agonist on PGHS-1 expression. We also discovered that induction of PGE2 biosynthesis in response to IL-1 or IL-1/FGF-1 was affected by the density of MG-63 cells in culture. Subconfluent cultures displayed a 3- to 10-fold greater response to IL-1 or IL-1/FGF-1 than confluent cultures. The decreased PGE2 induction by IL-1 in confluent cultures was associated with reduced IL-1 receptor expression. We conclude that the signaling pathways resulting in PGE2 biosynthesis in response to proinflammatory agents like IL-1 are subject to complex regulation by additional soluble mediators as well as cell–cell or cell–extracellular matrix interactions.