A novel role for the Rho-associated kinase, ROCK, in IL-1-stimulated intestinal epithelial cell responses

作者：Rafferty Brian J; Unger Benjamin L; Perey Aaron C; Tammariello Steven P; Pavlides Savvas; McGee Dennis W^*

来源：Cellular Immunology, 2012, 280(2): 148-155.

DOI：10.1016/j.cellimm.2012.12.003

• IL-1
• Intestinal epithelial
• CXCL8
• JNK
• CCL2
• ROCK

Intestinal epithelial cells (IEC) play a role in mucosal inflammation by producing pro-inflammatory chemokines that may initiate or amplify local responses. IL-1 is a potent activator of IEC and its receptor localizes to focal adhesions. Since the Rho-associated kinase, ROCK, also localizes to focal adhesions, we examined the role of ROCK in IL-1-induced chemokine responses in IEC cell lines. Suppressing ROCK with the Y27632 inhibitor suppressed IL-1-stimulated Caco-2 cell CXCL8/IL-8 and IEC-6 cell CCL2/MCP-1 secretion and mRNA levels. ROCK inhibition also suppressed IL-1-induced JNK phosphorylation in both cell lines, but high levels of the inhibitor had no significant effect on IL-1-stimulated Caco-2 I kappa B alpha phosphorylation and degradation or IKK phosphorylation and kinase activity. Therefore, ROCK may exert an effect on IL-1-stimulated JNK signaling to AP-1 activation, with little effect on IKK/I kappa B alpha, signaling, defining a potentially important mechanism for regulating IL-1 signaling in IEC that may be essential for optimal cytokine responses.

• 出版日期2012-12