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Am J Physiol Gastrointest Liver Physiol 282: G77-G85, 2002; doi:10.1152/ajpgi.00031.2002
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Vol. 282, Issue 1, G77-G85, January 2002

MCP-1 but not CINC synthesis is increased in rat pancreatic acini in response to cerulein hyperstimulation

Madhav Bhatia1, Mark Brady1, Yun Kyung Kang1, Eithne Costello1, Darren J. Newton2, Stephen E. Christmas2, John P. Neoptolemos1, and John Slavin1

Departments of 1 Surgery and 2 Immunology, University of Liverpool, Royal Liverpool University Hospital, Liverpool L69 3GA, United Kingdom

Inflammatory mediators including chemokines play a critical role in acute pancreatitis. The precise nature of early inflammatory signals within the pancreas remains, however, unclear. We examined the ability of isolated pancreatic acini to synthesize CC chemokine monocyte chemotactic protein-1 (MCP-1) and CXC chemokine cytokine-induced neutrophil chemoattractant (CINC) and the response to the secretagogue cerulein at physiological and supraphysiological concentrations. Isolated rat pancreatic acini maintained in short-term (<= 48 h) primary culture constitutively synthesized MCP-1 and CINC. Cerulein (10-7 M; supramaximal dose) increased production of MCP-1 but not CINC. Cerulein-induced increase in MCP-1 synthesis was accompanied by increase in nuclear factor (NF)-kappa B activation shown by EMSA. Pretreatment with NF-kappa B inhibitors N-acetylcysteine (NAC) and N-tosylphenyalanine chloromethyl ketone (TPCK) blocked cerulein-induced NF-kappa B activation and abolished cerulein's effect on MCP-1 synthesis. Pretreatment with calcium antagonist BAPTA-AM also blocked cerulein's effect on MCP-1 synthesis. These results indicate that isolated acini synthesize MCP-1 and CINC and support the idea of acinar-derived chemokines as early mediators of inflammatory response in acute pancreatitis. Although cerulein hyperstimulation increased MCP-1 synthesis by a calcium-dependent mechanism involving NF-kappa B activation, CINC synthesis was not affected. This suggests that regulation of CC and CXC chemokines within acinar cells may be quite different.

monocyte chemotactic protein-1; cytokine-induced neutrophil chemoattractant; nuclear factor-kappa B.


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