title: Activation of the alpha3 integrin affects TRAF6 function in the IL-1 signaling pathway of CACO-2 epithelial cells.
abstract: 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.
authors.affiliation: Department of Biological Sciences, Binghamton University (SUNY), Binghamton, New York 13902-6000, USA.
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Rafferty
authors.forename: Gongchu
authors.initials: G
authors.lastname: Li
authors.forename: Dennis W
authors.initials: DW
authors.lastname: McGee
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D018938:Caco-2 Cells; D006801:Humans; D018928:Immunity, Mucosal; D039422:Integrin alpha3 / Q000276:immunology*; D007375:Interleukin-1 / Q000276:immunology / Q000378:metabolism; D053592:Interleukin-1 Receptor-Associated Kinases / Q000378:metabolism; D007413:Intestinal Mucosa / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D020930:MAP Kinase Kinase Kinases / Q000378:metabolism; D010766:Phosphorylation; D011485:Protein Binding / Q000187:drug effects / Q000276:immunology; D017472:Receptors, Interleukin-1 / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects* / Q000276:immunology; D048029:TNF Receptor-Associated Factor 6 / Q000378:metabolism*; D000099151:MAP Kinase Kinase Kinase 7
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000911:Antibodies, Monoclonal; D039422:Integrin alpha3; D007375:Interleukin-1; D053592:Interleukin-1 Receptor-Associated Kinases; D020930:MAP Kinase Kinase Kinases; D017472:Receptors, Interleukin-1; D048029:TNF Receptor-Associated Factor 6; D000099151:MAP Kinase Kinase Kinase 7; C410585:TAB2 protein, human