Activation of the α3 Integrin Affects TRAF6 Function In The IL-1 Signaling Pathway of CACO-2 Epithelial Cells

Abstract

Intestinal epithelial cells express the α3β1 integrin which binds to laminin-5. We have previously shown that activation of the α3 integrin through laminin-5 binding or a cross-linking antibody results in a suppression of IL-1 induced cytokine secretion and intracellular signaling through IKK to NF-κB and JNK to AP-1 in Caco-2 cells. In the present study, the effects of α3 integrin activation on the proximal events of IL-1 induced signaling were examined. Monoclonal antibody activation of the α3 integrin on Caco-2 cells prior to IL-1 stimulation had no effect on the association of the adapter protein TAB2 with TAK1. However, the association of TRAF6 with TAK1, and TRAF6 with the IL-1 receptor I was significantly suppressed. Activation of the α3 integrin had no effect on total levels of TRAF6. Finally, the IL-1 induced formation of higher molecular weight, presumably phosphorylated, forms of IRAK-1 were not altered by α3 integrin activation, suggesting that signaling events leading up to IRAK-1 were unaffected. These results suggest that the suppressive effects of α3 integrin activation on IL-1 signaling may be due to an effect on the function of TRAF6, preventing the transmission of the signal from the IL-1RI complex to the TAK1 complex.