Aspirin effects on gastric epithelial cell proliferation and cytokine expression

Aspirin is known to cause gastric injury and to delay ulcer healing. The ef fects of aspirin on gastric epithelial cell function are heterogeneous; in contrast to injuring the mucosa, aspirin may also act beneficially by induc ing adaptation; a mechanism that is poorly understood. We aimed to document the effects of different doses of aspirin on gastric epithelial cell funct ion defined as proliferation, and secretion as well as mRNA expression of c ytokines. Furthermore, we studied the effects of aspirin pretreatment on cy tokine secretion as a potential element of gastric adaptation. The prolifer ative activity of three different gastric epithelial cell lines (AGS, KATO III, RGM-1) was assessed by H-3-thymidine incorporation; secretion of growt h factors PDGF-AB and VEGF into culture supernatant was documented by ELISA . mRNA transcripts of both cytokines were quantified by real time RT-PCR. L ow doses of aspirin did not alter the proliferative dynamics in two of the three studied cell lines; high doses abolished proliferation. Secretion of PDGF-AB and VEGF increased during the first days of low dose apirin exposit ion; higher concentrations led to a depletion of cytokines after an initial liberation in the case of VEGF, mRNA of which was also dose-dependently in creased by aspirin. Seven-day pretreatment with low amounts of aspirin did not alter the secretory response of the epithelia caused by higher doses of this drug. The secretion of cytokines and proliferation of gastric epithel ial cells are adversely effected by aspirin in a similarly dose-dependent f ashion as the intended effects of this drug on platelet function and pain r elief. (C) 2001 Wiley-Liss. Inc.