title: MCP-1 but not CINC synthesis is increased in rat pancreatic acini in response to cerulein hyperstimulation.
abstract: 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 (< or =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)-kappaB activation shown by EMSA. Pretreatment with NF-kappaB inhibitors N-acetylcysteine (NAC) and N-tosylphenyalanine chloromethyl ketone (TPCK) blocked cerulein-induced NF-kappaB 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-kappaB activation, CINC synthesis was not affected. This suggests that regulation of CC and CXC chemokines within acinar cells may be quite different.
authors.affiliation: Department of Surgery, University of Liverpool, Royal Liverpool University Hospital, Liverpool L69 3GA, United Kingdom.
authors.forename: Madhav
authors.initials: M
authors.lastname: Bhatia
authors.forename: Mark
authors.initials: M
authors.lastname: Brady
authors.forename: Yun Kyung
authors.initials: YK
authors.lastname: Kang
authors.forename: Eithne
authors.initials: E
authors.lastname: Costello
authors.forename: Darren J
authors.initials: DJ
authors.lastname: Newton
authors.forename: Stephen E
authors.initials: SE
authors.lastname: Christmas
authors.forename: John P
authors.initials: JP
authors.lastname: Neoptolemos
authors.forename: John
authors.initials: J
authors.lastname: Slavin
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D000681:Amylases / Q000378:metabolism; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002470:Cell Survival; D002478:Cells, Cultured; D002108:Ceruletide / Q000494:pharmacology*; D002614:Chelating Agents / Q000494:pharmacology; D018932:Chemokine CCL2 / Q000032:analysis / Q000096:biosynthesis*; D019743:Chemokines, CXC; D002630:Chemotactic Factors / Q000032:analysis / Q000096:biosynthesis*; D004533:Egtazic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016166:Free Radical Scavengers / Q000494:pharmacology; D006133:Growth Substances / Q000032:analysis / Q000096:biosynthesis*; D036341:Intercellular Signaling Peptides and Proteins; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D010179:Pancreas / Q000737:chemistry / Q000166:cytology / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology; D019284:Thapsigargin / Q000494:pharmacology; D014108:Tosylphenylalanyl Chloromethyl Ketone / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D002614:Chelating Agents; D018932:Chemokine CCL2; D019743:Chemokines, CXC; D002630:Chemotactic Factors; D004791:Enzyme Inhibitors; D016166:Free Radical Scavengers; D006133:Growth Substances; D036341:Intercellular Signaling Peptides and Proteins; D016328:NF-kappa B; D015842:Serine Proteinase Inhibitors; D014409:Tumor Necrosis Factor-alpha; C070379:1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid acetoxymethyl ester; D014108:Tosylphenylalanyl Chloromethyl Ketone; D004533:Egtazic Acid; D019284:Thapsigargin; D002108:Ceruletide; D000681:Amylases; D002118:Calcium; D000111:Acetylcysteine