α3β1 integrin induced suppression of the Caco-2 epithelial cell IL-1 signaling pathway leading to NF-κB activation

Intestinal epithelial cells (IECs) produce several potent cytokines in response to interleukin-1 (IL-1) and may play a role in the inflammatory response. Previously, we determined that treatment of the Caco-2 cells with a cross-linking anti-alpha 3 integrin antibody resulted in a suppression of IL-1 induced cytokine secretion and mRNA levels, suggesting that the alpha 3 beta 1 integrin may play a role in the regulation of IEC cytokine responses to IL-1. In this report, treatment of the Caco-2 cells with the anti-alpha 3 integrin antibody resulted in a suppression of IL-1 induced levels of NF-kappa B binding activity in nuclear extracts, as determined by EMSA, as well as phosphorylation and degradation of the Inhibitor, I kappa B alpha. The anti-integrin antibody treatment was also found to Suppress I kappa B kinase (IKK) activity and IKK beta phosphorylation. Culture of the Caco-2 cells on purified laminin-5, the ligand for the alpha 3 beta 1 integrin, also resulted in suppression of IL-1 induced phosphorylation of I kappa B alpha and IKK beta. Together with our previous findings, these results suggest that alpha 3 beta 1 integrin binding results in a suppression of the IL-1 signaling pathway leading to the activation of NF-kappa B and ultimately IEC cytokine responses. These studies define a novel regulatory mechanism which may be important in the control of IEC cytokine responses during inflammation. (c) 2004 Elsevier Inc. All rights reserved.