title: The role of redox status on chemokine expression in acute pancreatitis.
abstract: This study focused on the involvement of oxidative stress in the mechanisms mediating chemokine production in different cell sources during mild and severe acute pancreatitis (AP) induced by bile-pancreatic duct obstruction (BPDO) and 3.5% NaTc, respectively. N-Acetylcysteine (NAC) was used as antioxidant treatment. Pancreatic glutathione depletion, acinar overexpression of monocyte chemoattractant protein-1 (MCP-1) and cytokine-induced neutrophil chemoattractant (CINC), and activation of p38MAPK, NF-kappaB and STAT3 were found in both AP models. NAC reduced the depletion of glutathione in BPDO- but not in NaTc-induced AP, in which oxidative stress overwhelmed the antioxidant capability of NAC. As a result, inhibition of the acinar chemokine expression and signalling pathways occurs in mild, but not in severe AP. However, MCP-1 and CINC expressions in whole pancreas and plasma chemokine levels were not reduced by NAC, even in BPDO-induced AP, suggesting that in addition to acini, other pancreatic cells produced chemokines by antioxidant resistant mechanisms. The high Il-6 plasma levels found during AP, both in NAC-treated and non-treated rats, pointed out cytokines as activating factors of chemokine expression in non-acinar cells. In conclusion, from early AP oxidant-mediated MAPK, NF-kappaB and STAT3 activation triggers the chemokine expression in acini but not in non-acinar cells.
authors.affiliation: Department of Physiology and Pharmacology, University of Salamanca, 37007 Salamanca, Spain.
authors.forename: S
authors.initials: S
authors.lastname: Yubero
authors.forename: L
authors.initials: L
authors.lastname: Ramudo
authors.forename: M A
authors.initials: MA
authors.lastname: Manso
authors.forename: I
authors.initials: I
authors.lastname: De Dios
mesh_terms: D000818:Animals; D018925:Chemokines / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D010084:Oxidation-Reduction; D010195:Pancreatitis / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D018925:Chemokines; D015850:Interleukin-6; D016328:NF-kappa B; D012333:RNA, Messenger; D048051:p38 Mitogen-Activated Protein Kinases