Effect of the alpha3beta1 integrin on the IL-1 stimulated activation of c-Jun N-terminal kinase (JNK) in CACO-2 cells.
Intestinal epithelial cells (IEC) are capable of responding to IL-1 stimulation by producing a variety of pro-inflammatory cytokines. Recently, we have found that binding of the alpha3beta1 integrin may have a regulatory effect on IL-1 responses and intracellular signaling by suppressing cytokine secretion, mRNA expression and the downstream intracellular signaling events from IKK to NF-kappaB activation. In this study, we extend these findings by showing that treatment of the Caco-2 epithelial cells with a cross-linking anti-alpha3 integrin antibody resulted in a suppression in the levels of IL-1 induced AP-1 binding activity in nuclear extracts. Furthermore, suppressed levels of IL-1 induced c-Jun N-terminal kinase (JNK) phosphorylation and kinase activity were seen with the antibody treated cells. Cells cultured on purified laminin-5, the ligand for the alpha3beta1 integrin, did not show significantly elevated levels of JNK phosphorylation after IL-1 stimulation while cells cultured on fibronectin yielded significantly elevated levels of IL-1 induced JNK phosphorylation. These results indicate that binding of the alpha3beta1 integrin results in a suppression in the activation of the IL-1 induced intracellular signaling pathway from JNK to AP-1. This novel regulatory effect may be a potentially important mechanism to regulate IL-1 mediated responses by IEC.
Stulic
Mate
M
Department of Biological Sciences, Binghamton University (SUNY), Binghamton, NY 13902-6000, USA.
Lubin
Farah D
FD
O'Donnell
Phyllis M
PM
Tammariello
Steven P
SP
McGee
Dennis W
DW
D000818:Animals; D018938:Caco-2 Cells; D015815:Cell Adhesion Molecules / Q000378:metabolism; D004789:Enzyme Activation; D005353:Fibronectins / Q000378:metabolism; D006801:Humans; D039201:Integrin alpha3beta1 / Q000378:metabolism*; D007375:Interleukin-1 / Q000378:metabolism*; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D018808:Transcription Factor AP-1 / Q000235:genetics / Q000378:metabolism; D000097794:Kalinin
D015815:Cell Adhesion Molecules; D005353:Fibronectins; D039201:Integrin alpha3beta1; D007375:Interleukin-1; D048031:JNK Mitogen-Activated Protein Kinases; D018808:Transcription Factor AP-1; D000097794:Kalinin