BACKGROUND: Different cytokines, including epidermal growth factor (EGF) and interleukin 1 beta (IL 1 beta), participate in the pathogenesis of gastric mucosal damage and repair by means of different mechanisms that are either paracrine or autocrine in nature. AIMS: To study whether EGF and IL 1 beta affect pepsinogen secretion in vitro. METHODS: Dispersed human peptic cells were prepared from endoscopically obtained biopsy specimens after collagenase digestion, mechanical disruption, and density gradient centrifugation. RESULTS: EGF dose dependently increased basal pepsinogen secretion and mitogenic concentrations (0.1 nM) of EGF induced submaximal stimulation. Similar effects were observed with transforming growth factor alpha. EGF effects on pepsinogen secretion were in addition to that induced by CCK-OP and db-cAMP stimulated pepsinogen secretion. EGF stimulated pepsinogen secretion was completely inhibited by a human immunospecific EGF receptor antibody and reduced by both genistein and tyrphostin-25, two different tyrosine kinase inhibitors. IL 1 beta does not affect basal, CCK-OP or acetylcholine stimulated pepsinogen secretion. However, IL 1 beta dose dependently inhibited db-cAMP and histamine stimulated pepsinogen secretion. CONCLUSIONS: These results show that both EGF and IL 1 beta modulate human pepsinogen secretion in vitro and suggest that the paracrine effects of these cytokines on pepsinogen secretion might be involved in some pathological conditions of damage and inflammation of the gastric mucosa.
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