title: Aspirin effects on gastric epithelial cell proliferation and cytokine expression.
abstract: Aspirin is known to cause gastric injury and to delay ulcer healing. The effects of aspirin on gastric epithelial cell function are heterogeneous; in contrast to injuring the mucosa, aspirin may also act beneficially by inducing adaptation; a mechanism that is poorly understood. We aimed to document the effects of different doses of aspirin on gastric epithelial cell function defined as proliferation, and secretion as well as mRNA expression of cytokines. Furthermore, we studied the effects of aspirin pretreatment on cytokine secretion as a potential element of gastric adaptation. The proliferative activity of three different gastric epithelial cell lines (AGS, KATO III, RGM-1) was assessed by (3)H-thymidine incorporation; secretion of growth factors PDGF-AB and VEGF into culture supernatant was documented by ELISA. mRNA transcripts of both cytokines were quantified by real time RT-PCR. Low 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 aspirin exposition; higher concentrations led to a depletion of cytokines after an initial liberation in the case of VEGF, mRNA of which was also dose-dependently increased 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 epithelial cells are adversely effected by aspirin in a similarly dose-dependent fashion as the intended effects of this drug on platelet function and pain relief.
authors.affiliation: Department of Medicine B, University of Münster, Münster, Germany. pohlet@uni-muenster.de
authors.forename: T
authors.initials: T
authors.lastname: Pohle
authors.forename: J C
authors.initials: JC
authors.lastname: Becker
authors.forename: A
authors.initials: A
authors.lastname: Markmann
authors.forename: N
authors.initials: N
authors.lastname: Lügering
authors.forename: H G
authors.initials: HG
authors.lastname: Pauels
authors.forename: J W
authors.initials: JW
authors.lastname: Konturek
authors.forename: W
authors.initials: W
authors.lastname: Domschke
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology* / Q000633:toxicity; D001241:Aspirin / Q000494:pharmacology* / Q000633:toxicity; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D016207:Cytokines / Q000096:biosynthesis / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D016228:Endothelial Growth Factors / Q000096:biosynthesis / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005753:Gastric Mucosa / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D008222:Lymphokines / Q000096:biosynthesis / Q000378:metabolism; D010982:Platelet-Derived Growth Factor / Q000096:biosynthesis / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D016207:Cytokines; D016228:Endothelial Growth Factors; D008222:Lymphokines; D010982:Platelet-Derived Growth Factor; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; C095477:platelet-derived growth factor AB; D001241:Aspirin