Effect of the alpha 3 beta 1 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 alpha 3 beta 1 integrin may have a regulatory effect on IL-1 responses and intracellular signaling by suppressing cytokine...

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Published in:Cytokine (Philadelphia, Pa.) Pa.), 2007-02, Vol.37 (2), p.163-170
Main Authors: Stulic, Mate, Lubin, Farah D, O'Donnell, Phyllis M, Tammariello, Steven P, McGee, Dennis W
Format: Article
Language:English
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Summary: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 alpha 3 beta 1 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- mu B activation. In this study, we extend these findings by showing that treatment of the Caco-2 epithelial cells with a cross-linking anti- alpha 3 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 alpha 3 beta 1 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 alpha 3 beta 1 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.
ISSN:1043-4666
DOI:10.1016/j.cyto.2007.03.010