Endogenous IL-1 and type II IL-1 receptor expression modulate anoikis in intestinal epithelial cells

We previously reported that IL-1β and the decoy receptor for IL-1 (IL-1RII) are expressed by intestinal epithelial cells (IEC) during detachment-induced cell death, or "anoikis." We now investigated whether IL-1 regulates anoikis. Skewing the balance in favor of IL-1, by blocking IL-1RII or by adding IL-1β to detached rat IEC-18 cells, reduced cell death. The protective effect of anti-IL-1RII was reversed by blocking IL-1β, confirming the anti-apoptotic effect was due to endogenous IL-1β. Added IL-1β also rescued cells from anoikis and was associated with considerable aggregation of the detached cells. Aggregate formation and the anti-apoptotic effect of added IL-1β were prevented by blocking E-cadherin, indicating that IL-1 promoted aggregation and indirectly, survival. On the other hand, treating detached cells with IL-1β and an anti-β₁ integrin antibody abolished the protective effect of IL-1β but not the aggregates. We conclude that the anti-apoptotic effect of IL-1 is mediated through a β₁ integrin-dependent event secondary to cell-cell adhesion. This illustrates a previously uncharacterized role for IL-1 in the intestine wherein this cytokine may facilitate the preservation of the epithelial monolayer integrity.