The Journal of Immunology, Vol 146, Issue 8 2633-2638, Copyright © 1991 by American Association of Immunologists

ARTICLES

Effects of transforming growth factor-beta and IL-1 alpha on prostaglandin synthesis in serum-deprived osteoblastic cells

A Marusic, JF Kalinowski, JR Harrison, M Centrella, LG Raisz and JA Lorenzo
Veterans Administration Medical Center, Newington, CT 06111.

We investigated the effects that the combination of IL-1 alpha and transforming growth factor-beta (TGF-beta) had on PGE2 production in a murine clonal osteoblastic cell line MC3T3-E1 and primary rat calvarial osteoblast-like cells. In serum-supplemented medium, IL-1 alpha was a potent stimulator of PGE2 production in MC3T3-E1 cells (50-fold increase with 0.1 ng/ml). TGF-beta (10 ng/ml) had only a small effect alone and no additional effect on IL-1 alpha-induced responses. In serum-deprived MC3T3-E1 cells, PGE2 responses to IL-1 alpha were either absent or markedly reduced. TGF-beta alone had small effects. However, simultaneous addition of TGF-beta with IL-1 alpha to MC3T3-E1 cells partially restored the ability of IL-1 alpha to generate a PGE2 response (10-fold increase in PGE2 with 0.1 ng/ml of both IL-1 alpha and TGF-beta). As with MC3T3-E1 cells, serum-deprived primary fetal rat calvarial osteoblastic cells also did not respond to IL-1 alpha, unless TGF-beta was present in the medium (sixfold increase in PGE2 with 0.1 ng/ml IL-1 alpha and 10 ng/ml TGF-beta). The synergistic effect of TGF- beta and IL-1 alpha was specific for PGE2 responses, because these factors did not synergistically affect cell proliferation, collagen and noncollagen protein synthesis, or alkaline phosphatase activity. The observed synergy was not associated with changes in the steady state cyclooxygenase (PGH synthase) mRNA levels. However, it did correlate with increased release of [3H]arachidonic acid from prelabeled serum- depleted MC3T3-E1 cells. Hence, the synergistic interactions of IL-1 alpha and TGF-beta on PGE2 appear to occur through an increase in the release of arachidonic acid substrate from phospholipid pools. These effects may be important for both normal bone turnover and the responses of bone to inflammatory and immune stimuli.

This article has been cited by other articles:

				L. Bouchard, R. de Medicis, A. Lussier, P. H. Naccache, and P. E. Poubelle Inflammatory Microcrystals Alter the Functional Phenotype of Human Osteoblast-Like Cells In Vitro: Synergism with IL-1 to Overexpress Cyclooxygenase-2 J. Immunol., May 15, 2002; 168(10): 5310 - 5317. [Abstract] [Full Text] [PDF]

				J. Pfeilschifter, R. Koditz, M. Pfohl, and H. Schatz Changes in Proinflammatory Cytokine Activity after Menopause Endocr. Rev., February 1, 2002; 23(1): 90 - 119. [Abstract] [Full Text] [PDF]

				T. J. Gal, T. Munoz-Antonia, C. A. Muro-Cacho, and D. W. Klotch Radiation Effects on Osteoblasts In Vitro: A Potential Role in Osteoradionecrosis Arch Otolaryngol Head Neck Surg, September 1, 2000; 126(9): 1124 - 1128. [Abstract] [Full Text] [PDF]

				C. Pilbeam, Y. Rao, O. Voznesensky, H. Kawaguchi, C. Alander, L. Raisz, and H. Herschman Transforming Growth Factor-{beta}1 Regulation of Prostaglandin G/H Synthase-2 Expression in Osteoblastic MC3T3-E1 Cells Endocrinology, November 1, 1997; 138(11): 4672 - 4682. [Abstract] [Full Text] [PDF]

				Q.-R. Chen, C. Miyaura, S. Higashi, M. Murakami, I. Kudo, S. Saito, T. Hiraide, Y. Shibasaki, and T. Suda Activation of Cytosolic Phospholipase A2 by Platelet-derived Growth Factor Is Essential for Cyclooxygenase-2-dependent Prostaglandin E2 Synthesis in Mouse Osteoblasts Cultured with Interleukin-1 J. Biol. Chem., February 28, 1997; 272(9): 5952 - 5958. [Abstract] [Full Text] [PDF]

				M. J. Thomas, Y. Umayahara, H. Shu, M. Centrella, P. Rotwein, and T. L. McCarthy Identification of the cAMP Response Element That Controls Transcriptional Activation of the Insulin-like Growth Factor-I Gene by Prostaglandin E2 in Osteoblasts J. Biol. Chem., September 6, 1996; 271(36): 21835 - 21841. [Abstract] [Full Text] [PDF]

				T. L. McCarthy, S. Casinghino, D. W. Mittanck, C.-H. Ji, M. Centrella, and P. Rotwein Promoter-dependent and -independent Activation of Insulin-like Growth Factor Binding Protein-5 Gene Expression by Prostaglandin E(2) in Primary Rat Osteoblasts J. Biol. Chem., March 22, 1996; 271(12): 6666 - 6671. [Abstract] [Full Text] [PDF]

				Y. Gu and S. J. Publicover Expression of Functional Metabotropic Glutamate Receptors in Primary Cultured Rat Osteoblasts. CROSS-TALK WITH N-METHYL-D-ASPARTATE RECEPTORS J. Biol. Chem., October 27, 2000; 275(44): 34252 - 34259. [Abstract] [Full Text] [PDF]