TGF-alpha reduces bradykinin-stimulated ion transport and prostaglandin release in human colonic epithelial cells

The effect of chronic exposure to transforming growth factor-alpha (TGF-alp ha) on bradykinin-stimulated acute prostanoid production and ion secretion in monolayers of HCA-7 colony 29 colonic epithelial cells has been studied. Monolayers synthesized prostaglandin E-2 (PGE(2)) at a basal rate of 2.10 +/- 0.31 pg.monolayer(-1).min(-1) over 24 h. Bradykinin (10(-8)-10(-5) M) d ose dependently increased acute PGE(2) release by three orders of magnitude . This was associated with a rise in cAMP from 1.60 +/- 0.14 to 2.90 +/- 0. 1 pmol/monolayer (P < 0.02) and a dose-dependent increase in short-circuit current (SCC). When monolayers were primed by a 24-h exposure to TGF-alpha, basal PGE(2) release rose to 6.31 +/- 0.38 pg.monolayer(-1).min(-1) (TGF-a lpha concn 10 ng/ml; P = 0.001). However, the stimulation of acute prostagl andin release,intracellular cAMP, and increased SCC by bradykinin was signi ficantly reduced by preincubation with TGF-alpha. Priming with PGE(2) (10(- 8)-10(-6) M) over 24 h mimicked the effect of TGF-alpha on bradykinin-induc ed changes in cAMP and SCC. These data suggest that enhanced chronic releas e of prostaglandins in response to stimulation with TGF-alpha may downregul ate acute responses to bradykinin. In vivo, TGF-alpha could have an importa nt modulatory function in regulating secretion under inflammatory condition s.