Transforming growth factor β1 augments mitogen-induced prostaglandin synthesis and expression of the TIS10/prostaglandin synthase 2 gene both in swiss 3T3 cells and in murine embryo fibroblasts
✍ Scribed by Rebecca S. Gilbert; Srinivasa T. Reddy; Dr. Dean A. Kujubu; Weilin Xie; Dr. Steven Luner; Harvey R. Herschman
- Publisher
- John Wiley and Sons
- Year
- 1994
- Tongue
- English
- Weight
- 1010 KB
- Volume
- 159
- Category
- Article
- ISSN
- 0021-9541
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✦ Synopsis
Abstract
Transforming growth factor‐beta (TGF‐beta), a potent cytokine, modulates a wide variety of biological responses. Among its actions, TGF‐beta can augment prostaglandin synthesis in several cell types. Although TGF‐beta alone has no effect on prostaglandin production in Swiss 3T3 cells, we find that TGF‐beta augments the ability of tetradecanoyl phorbol acetate (TPA) or serum to stimulate PGE~2~ production. The TIS10 gene is a primary response gene encoding a second form of prostaglandin synthase (PGS), the rate‐limiting enzyme in the biosynthesis of prostaglandins, thrornboxanes, and prostacyclins from arachidonic acid. TIS10/PGS‐2 expression is induced by mitogens in Swiss 3T3 cells. TGF‐beta also augments mitogen‐induced synthesis and accumulation of TIS10/PGS‐2 protein and induction of TIS10/PGS‐2 message in Swiss 3T3 cells. In contrast, TGF‐beta has little or no effect on the level of PGS‐1 (EC1.14.99.1) message, either alone or in concert with TPA or serum. TGF‐beta concentrations in the range of 0.01–0.10 ng/ml (0.4–4.0 pM) maximally enhance mitogen induction of TIS10/PGS‐2 message. TPA‐induced accumulation of unspliced TIS10/PGS‐2 transcript is augmented by TGF‐beta, suggesting that this cytokine exerts its effect on expression of the TIS10/PGS‐2 gene by transcriptional regulation. TGF‐beta also augments TPA‐induced prostaglandin production, TIS10/PGS‐2 antigen accumulation, and TIS10/PGS‐2 message induction in primary cultures of mouse embryo fibroblasts. Dexamethasone attenuates TGF‐beta enhancement of all these mitogen‐induced responses: PGE~2~ accumulation, appearance of TIS10/PGS‐2 protein and message, and accumulation of TIS10/PGS‐2 unprocessed transcript. © 1994 wiley‐Liss, Inc.