Transforming growth factor beta 1 augments mitogen-induced prostaglandin synthesis and expression of the TIS10/prostaglandin synthase 2 gene both in Swiss 3T3 cells and in murine embryo fibroblasts

J Cell Physiol. 1994 Apr;159(1):67-75. doi: 10.1002/jcp.1041590110.


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 PGE2 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, thromboxanes, 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: PGE2 accumulation, appearance of TIS10/PGS-2 protein and message, and accumulation of TIS10/PGS-2 unprocessed transcript.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 3T3 Cells / enzymology*
  • Animals
  • Base Sequence
  • Cells, Cultured
  • Dexamethasone / pharmacology
  • Dinoprostone / metabolism
  • Embryo, Mammalian / cytology
  • Embryo, Mammalian / metabolism*
  • Fibroblasts / cytology
  • Fibroblasts / metabolism*
  • Gene Expression Regulation, Enzymologic / genetics*
  • Mice
  • Mice, Inbred BALB C
  • Mitogens / pharmacology*
  • Molecular Sequence Data
  • Prostaglandin-Endoperoxide Synthases / genetics*
  • Prostaglandins / biosynthesis*
  • RNA, Messenger / analysis
  • RNA, Messenger / genetics
  • Serum Albumin / pharmacology
  • Tetradecanoylphorbol Acetate / pharmacology
  • Transcription, Genetic
  • Transforming Growth Factor beta / pharmacology*


  • Mitogens
  • Prostaglandins
  • RNA, Messenger
  • Serum Albumin
  • Transforming Growth Factor beta
  • Dexamethasone
  • Prostaglandin-Endoperoxide Synthases
  • Dinoprostone
  • Tetradecanoylphorbol Acetate