Gastric mucosal cell protection by epidermal growth factor in primary monolayer culture of guinea pig gastric mucous cells

Background. Epidermal growth factor (EGF) has an anti-ulcer effect, but the mechanisms of this gastric mucosal protection are incompletely understood. We have suggested the importance of mucin as a mucosal protectant. We investigated whether increased mucin biosynthesis might be involved in the gastric mucosal protection conferred by EGF. Methods. EGF and then ethanol were added to primary monolayer cultures of guinea pig gastric mucous cells, in which factors such as gastric acid and gastrointestinal hormones were excluded. Mucin and prostaglandin E2 (PGE2) were assayed. Results. Cytoprotection induced by EGF was demonstrated. Mucin biosynthesis and PGE2 release were both significantly increased by EGF. When endogenous PGE2 synthesis was inhibited by pretreatment with 10−5 M or 10−4 M indomethacin (IND), mucin biosynthesis was still significantly increased by EGF. Ethanol-induced cell damage was concentration-dependent in cultures with no other additions (normal PGE2 and mucin biosynthesis). Damage by ethanol was decreased by EGF pretreatment (increased PGE2 and mucin biosynthesis). Damage by ethanol was increased by 10−5 M IND pretreatment (decreased PGE2; normal mucin biosynthesis) and by 10−4 M IND pretreatment (decreased PGE2 and mucin biosynthesis). Ethanol-induced damage was decreased by EGF pretreatment even in the presence of 10−5 M and 10−4 M IND (decreased PGE2; increased mucin biosynthesis). Conclusions. Increased mucin biosynthesis, induced by EGF independently of PGE2, protects gastric mucous cells.