HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 291/3/G432    most recent 00579.2005v2 00579.2005v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (9) Citing Articles via Google Scholar Google Scholar Articles by Satoh, A. Articles by Pandol, S. J. Search for Related Content PubMed PubMed Citation Articles by Satoh, A. Articles by Pandol, S. J.

INFLAMMATION/IMMUNITY/MEDIATORS

Ethanol sensitizes NF-B activation in pancreatic acinar cells through effects on protein kinase C-

¹Research Center for Alcoholic Liver and Pancreatic Diseases, Veterans Affairs Greater Los Angeles Health Care System and University of California, Los Angeles, California; and ²Division of Gastroenterology, Tohoku University Graduate School of Medicine, Seiryo-Machi, Sendai, Japan

Submitted 21 December 2005 ; accepted in final form 19 March 2006

Although ethanol abuse is the most common cause of pancreatitis, the mechanism of alcohol's effect on the pancreas is not well understood. Previously, we demonstrated that in vitro ethanol treatment of pancreatic acinar cells augmented the CCK-8-induced activation of NF-B, a key signaling system involved in the inflammatory response of pancreatitis. In the present study, we determine the role for individual PKC isoforms in the sensitizing effect of ethanol on NF-B activation. Dispersed rat pancreatic acini were treated with and without ethanol and then stimulated with CCK-8; 100 nM CCK-8 caused both NF-B and PKC-, -, and - activation, whereas 0.1 nM CCK-8 did not increase PKC-, PKC-, or NF-B activity. CCK-8 (0.1 nM) did activate PKC-. PKC- activator alone did not cause NF-B activation; however, together with 0.1 nM CCK-8, it caused NF-B activation. Ethanol activated PKC- without affecting other PKC isoforms or NF-B activity. Of note, stimulation of acini with ethanol and 0.1 nM CCK-8 resulted in the activation of PKC-, PKC-, and NF-B. The NF-B activation to 0.1 nM CCK-8 in ethanol-pretreated acini was inhibited by both PKC- inhibitor and PKC- inhibitor. Taken together, these results demonstrate the different modes of activation of PKC isoforms and NF-B in acini stimulated with ethanol, high-dose CCK-8, and low-dose CCK-8, and furthermore suggest that activation of both PKC- and - is required for NF-B activation. These results suggest that ethanol enhances the CCK-8-induced NF-B activation at least in part through its effects on PKC-.

alcoholic pancreatitis; cholecystokinin; inflammatory response; protein kinase C- translocation activator

This article has been cited by other articles:

				J. Yuan, A. Lugea, L. Zheng, I. Gukovsky, M. Edderkaoui, E. Rozengurt, and S. J. Pandol Protein kinase D1 mediates NF-{kappa}B activation induced by cholecystokinin and cholinergic signaling in pancreatic acinar cells Am J Physiol Gastrointest Liver Physiol, December 1, 2008; 295(6): G1190 - G1201. [Abstract] [Full Text] [PDF]

				E. C. Thrower, S. Osgood, C. A. Shugrue, T. R. Kolodecik, A. M. Chaudhuri, J. R. Reeve Jr, S. J. Pandol, and F. S. Gorelick The novel protein kinase C isoforms -{delta} and -{varepsilon} modulate caerulein-induced zymogen activation in pancreatic acinar cells Am J Physiol Gastrointest Liver Physiol, June 1, 2008; 294(6): G1344 - G1353. [Abstract] [Full Text] [PDF]

				R. D. Ramnath, J. Sun, S. Adhikari, L. Zhi, and M. Bhatia Role of PKC-{delta} on substance P-induced chemokine synthesis in pancreatic acinar cells Am J Physiol Cell Physiol, March 1, 2008; 294(3): C683 - C692. [Abstract] [Full Text] [PDF]

				Z Rakonczay Jr, P Hegyi, T Takacs, J McCarroll, and A K Saluja The role of NF-{kappa}B activation in the pathogenesis of acute pancreatitis Gut, February 1, 2008; 57(2): 259 - 267. [Abstract] [Full Text] [PDF]

				T. T. Chiu, W. Y. Leung, M. P. Moyer, R. M. Strieter, and E. Rozengurt Protein kinase D2 mediates lysophosphatidic acid-induced interleukin 8 production in nontransformed human colonic epithelial cells through NF-{kappa}B Am J Physiol Cell Physiol, February 1, 2007; 292(2): C767 - C777. [Abstract] [Full Text] [PDF]