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.
Nakamura
E
E
Department of Applied Pharmacology, Kyoto Pharmaceutical University, Yamashina, Japan.
Takahashi
S
S
Matsui
H
H
Okabe
S
S
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D004247:DNA / Q000096:biosynthesis / Q000187:drug effects; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D005753:Gastric Mucosa / Q000187:drug effects* / Q000293:injuries / Q000473:pathology; D007375:Interleukin-1 / Q000494:pharmacology*; D051381:Rats; D013997:Time Factors; D016211:Transforming Growth Factor alpha / Q000494:pharmacology*
D007375:Interleukin-1; D016211:Transforming Growth Factor alpha; D004815:Epidermal Growth Factor; D004247:DNA