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: 294/3/C683    most recent 00360.2007v1 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 Google Scholar Google Scholar Articles by Ramnath, R. D. Articles by Bhatia, M. Search for Related Content PubMed PubMed Citation Articles by Ramnath, R. D. Articles by Bhatia, M.

RECEPTORS AND SIGNAL TRANSDUCTION

Role of PKC- on substance P-induced chemokine synthesis in pancreatic acinar cells

Department of Pharmacology, National University of Singapore, Singapore

Submitted 13 August 2007 ; accepted in final form 17 December 2007

Interaction of the neuropeptide substance P (SP) with its high-affinity neurokinin-1 receptor (NK1R) plays an important role in the pathophysiology of acute pancreatitis. SP is known to stimulate the production of chemokines monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory protein (MIP)-1, and MIP-2 in pancreatic acinar cells via the activation of NF-B. However, the signaling mechanisms by which the SP-NK1R interaction induces NF-B activation and chemokine production remain unclear. To that end, in the present study, we investigated the participation of PKC in SP-induced chemokine production in pancreatic acinar cells. In this study, we showed that SP stimulated an early phosphorylation of PKC isoform PKC- followed by increased activation of MAPKKK MEKK1 and MAPK ERK and JNK as well as transcription factor NF-B and activator protein-1 driven chemokine production. Depletion of PKC- with its inhibitor rottlerin or the specific PKC- translocation inhibitor peptide dose dependently decreased SP-induced PKC-, MEKK1, ERK, JNK, NF-B, and AP-1 activation. Moreover, rottlerin as well as PKC- translocation inhibitor inhibited SP-induced chemokine production in a concentration-dependent manner. We also demonstrated that PKC- activation was attenuated by CP96345, a selective NK1R antagonist, thus showing that PKC- activation was indeed mediated by SP in pancreatic acinar cells. These results show that PKC- is an important proinflammatory signal transducer for SP-NK1R-induced chemokine production in pancreatic acinar cells.

protein kinse C-; mitogen-activated protein kinase kinase kinase-1; extracellular signal-regulated kinase; c-Jun NH₂-terminal kinase; nuclear factor-B; activator protein-1

This article has been cited by other articles:

				J. Sun, R. D. Ramnath, R. Tamizhselvi, and M. Bhatia Role of protein kinase C and phosphoinositide 3-kinase-Akt in substance P-induced proinflammatory pathways in mouse macrophages FASEB J, April 1, 2009; 23(4): 997 - 1010. [Abstract] [Full Text] [PDF]