The role of redox status on chemokine expression in acute pancreatitis.
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.
Yubero
S
S
Department of Physiology and Pharmacology, University of Salamanca, 37007 Salamanca, Spain.
Ramudo
L
L
Manso
M A
MA
De Dios
I
I
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
D018925:Chemokines; D015850:Interleukin-6; D016328:NF-kappa B; D012333:RNA, Messenger; D048051:p38 Mitogen-Activated Protein Kinases