title: A novel role for the Rho-associated kinase, ROCK, in IL-1-stimulated intestinal epithelial cell responses.
abstract: 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 IκBα 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/IκBα signaling, defining a potentially important mechanism for regulating IL-1 signaling in IEC that may be essential for optimal cytokine responses.
authors: Department of Biological Sciences, Binghamton University (SUNY), Binghamton, NY 13902-6000, USA.
authors: Brian J
authors: BJ
authors: Rafferty
authors: Benjamin L
authors: BL
authors: Unger
authors: Aaron C
authors: AC
authors: Perey
authors: Steven P
authors: SP
authors: Tammariello
authors: Savvas
authors: S
authors: Pavlides
authors: Dennis W
authors: DW
authors: McGee
mesh_terms: D018938:Caco-2 Cells; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000502:physiology; D010766:Phosphorylation; D015398:Signal Transduction; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors / Q000502:physiology*
chemical_list: D007375:Interleukin-1; D016328:NF-kappa B; D054460:rho-Associated Kinases; D048031:JNK Mitogen-Activated Protein Kinases
references: Immunology. 2006 May;118(1):112-21
references: 16630028
references: Curr Opin Cell Biol. 2007 Apr;19(2):142-9
references: 17303404
references: Sci Signal. 2010 Jan 19;3(105):cm1
references: 20086235
references: J Biol Chem. 1995 Mar 17;270(11):6042-9
references: 7890736
references: Am J Physiol Cell Physiol. 2003 Nov;285(5):C1028-35
references: 12826601
references: Am J Respir Cell Mol Biol. 1999 Jun;20(6):1190-200
references: 10340938
references: J Invest Surg. 2007 Jan-Feb;20(1):23-33
references: 17365404
references: Gastroenterology. 1995 Jan;108(1):40-50
references: 7806062
references: Biochem J. 2000 Oct 1;351(Pt 1):95-105
references: 10998351
references: J Cell Biol. 2005 Aug 1;170(3):443-53
references: 16043513
references: Gastroenterology. 2003 May;124(5):1180-7
references: 12730857
references: Eur J Immunol. 1997 May;27(5):1091-7
references: 9174597
references: J Immunol. 1997 Jan 1;158(1):226-34
references: 8977194
references: J Neurosci. 2004 Mar 17;24(11):2837-45
references: 15028778
references: World J Gastroenterol. 2008 Jan 14;14(2):200-2
references: 18186555
references: Cell Immunol. 2004 Sep-Oct;231(1-2):30-9
references: 15919367
references: Cell Cycle. 2009 Jul 1;8(13):2110-21
references: 19502798
references: Nature. 2007 Mar 29;446(7135):557-61
references: 17361131
references: Mol Hum Reprod. 2007 Mar;13(3):181-7
references: 17227815
references: J Immunol. 1993 Jul 15;151(2):970-8
references: 8335922
references: Am J Physiol Cell Physiol. 2000 Mar;278(3):C451-62
references: 10712233
references: J Biol Chem. 2005 Mar 18;280(11):10624-35
references: 15611088
references: Gastroenterology. 1993 Dec;105(6):1689-97
references: 8253345
references: Mol Pharmacol. 2000 May;57(5):976-83
references: 10779382
references: Nature. 2007 Jul 26;448(7152):427-34
references: 17653185
references: Cancer Lett. 2007 Mar 8;247(1):1-25
references: 16725254
references: J Intern Med. 2008 Jun;263(6):591-6
references: 18479258
references: Proc Natl Acad Sci U S A. 2008 Sep 30;105(39):15058-63
references: 18815378
references: Arthritis Res. 2001;3(6):381-8
references: 11714393
references: Front Biosci. 1999 Mar 15;4:D310-21
references: 10077538
references: J Clin Invest. 1995 Jan;95(1):55-65
references: 7814646
references: FEBS Lett. 1996 Aug 26;392(2):189-93
references: 8772201
references: J Interferon Cytokine Res. 1999 May;19(5):429-38
references: 10386854
references: Arterioscler Thromb Vasc Biol. 2005 Sep;25(9):1831-6
references: 15994438
references: Int J Mol Med. 2006 Mar;17(3):449-55
references: 16465391