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.

ACKNOWLEDGMENTS

The authors would like to thank Benjamin Unger for his technical assistance in this study. This work was supported by U.S. PHS Grant DK54049.

Declaration of Interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper. Both BJR and GL contributed equally to this manuscript.