Rapid Expression of IL-1β by Intestinal Epithelial Cellsin Vitro

Abstract

Intestinal epithelial cells have been shown to produce IL-1βin vivo.This gene expression is rapid and precedes most determinants of inflammation, suggesting a pivotal role for IL-1β in the early events leading to inflammation. To better understand the mechanisms leading to this IL-1β production, we have developed anin vitromodel system employing a nontransformed intestinal epithelial cell line that does not constitutively express IL-1β. Following detachment, these cells rapidly expressed IL-1β mRNA. This expression was enhanced, but not induced, by LPS. IL-1β protein was detected by immunoprecipitation in the culture medium from passaged IEC-18 but not intracellularly, suggesting an efficient secretion of the molecule following induction. Interestingly, culture supernatants from passaged cells were without IL-1 bioactivity, suggesting the presence of an inhibitor as well. RT-PCR and Western blot analysis showed expression of IL-1RII by IEC-18 following detachment, possibly explaining the observed lack of bioactivity. These results indicate a novel pathway for IL-1β production and suggest that proinflammatory effects of IEC-derived IL-1 may be modulated by the simultaneous production of IL-1 antagonists.