Activation of the alpha3 integrin affects TRAF6 function in the IL-1 signaling pathway of CACO-2 epithelial cells.

Intestinal epithelial cells express the alpha3beta1 integrin which binds to laminin-5. We have previously shown that activation of the alpha3 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-kappaB and JNK to AP-1 in Caco-2 ...
cells. In the present study, the effects of alpha3 integrin activation on the proximal events of IL-1 induced signaling were examined. Monoclonal antibody activation of the alpha3 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 alpha3 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 alpha3 integrin activation, suggesting that signaling events leading up to IRAK-1 were unaffected. These results suggest that the suppressive effects of alpha3 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.
Mesh Terms:
Adaptor Proteins, Signal Transducing, Antibodies, Monoclonal, Caco-2 Cells, Humans, Immunity, Mucosal, Integrin alpha3, Interleukin-1, Interleukin-1 Receptor-Associated Kinases, Intestinal Mucosa, MAP Kinase Kinase Kinases, Phosphorylation, Protein Binding, Receptors, Interleukin-1, Signal Transduction, TNF Receptor-Associated Factor 6
Immunol. Invest.
Date: Jan. 13, 2010
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