Endogenous IL-1 and type II IL-1 receptor expression modulate anoikis in intestinal epithelial cells.
We previously reported that IL-1beta 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-1beta to detached rat IEC-18 cells, reduced cell death. The protective effect of anti-IL-1RII was reversed by blocking IL-1beta, confirming the anti-apoptotic effect was due to endogenous IL-1beta. Added IL-1beta 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-1beta were prevented by blocking E-cadherin, indicating that IL-1 promoted aggregation and indirectly, survival. On the other hand, treating detached cells with IL-1beta and an anti-beta(1) integrin antibody abolished the protective effect of IL-1beta but not the aggregates. We conclude that the anti-apoptotic effect of IL-1 is mediated through a beta(1) 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.
Waterhouse
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Department of Microbiology, Dalhousie University, Halifax, Nova Scotia, Canada.
Joseph
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Stadnyk
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D000818:Animals; D023102:Anoikis / Q000187:drug effects / Q000502:physiology*; D015820:Cadherins / Q000187:drug effects / Q000378:metabolism; D020169:Caspases / Q000187:drug effects / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology*; D002449:Cell Aggregation / Q000187:drug effects / Q000502:physiology; D002450:Cell Communication / Q000187:drug effects / Q000502:physiology*; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D007249:Inflammation / Q000378:metabolism / Q000503:physiopathology; D019012:Integrin beta1 / Q000187:drug effects / Q000378:metabolism; D007375:Interleukin-1 / Q000378:metabolism* / Q000494:pharmacology; D007413:Intestinal Mucosa / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D017472:Receptors, Interleukin-1 / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D053574:Receptors, Interleukin-1 Type II
D015820:Cadherins; D019012:Integrin beta1; D007375:Interleukin-1; D017472:Receptors, Interleukin-1; D053574:Receptors, Interleukin-1 Type II; D020169:Caspases