Interleukin-1beta inhibits growth factor-stimulated restoration of wounded rat gastric epithelial cell monolayers.

We examined the effect of interleukin-1beta (IL-1beta) on spontaneous and enhanced restoration (cell migration and proliferation) using an in vitro wound model comprising a confluent monolayer of rat gastric epithelial RGM1 cells. Repair of an artificial wound in a cell monolayer was found to be time- and concentration-dependent when the cells were incubated with epidermal growth factor (EGF) or transforming growth factor (TGF) -alpha alone for up to 24 hr. The growth factors also stimulated DNA synthesis significantly for 24 hr in a concentration-related manner. IL-1beta had no effect on wound restoration in the absence of the growth factors. However, it markedly inhibited the restoration enhanced by EGF and TGF-alpha, the inhibition being about 60% and 70%, respectively. In addition, IL-1beta significantly reduced the DNA synthesis stimulated by the growth factors. The EGF- and TGF-alpha-enhanced restoration was reduced by about 30% by mitomycin C, which potently inhibited the stimulated DNA synthesis. Mitomycin C had no effect on the spontaneous restoration. Even when treated with mitomycin C, the inhibitory effect of IL-1beta on the enhanced wound repair was still observed; however, the extent of the inhibition was decreased. These results indicate that IL-1beta inhibits the migration as well as the proliferation of gastric epithelial cells enhanced by EGF and TGF-alpha, resulting in a failure of wound healing.