Protein kinase C modulates the pulmonary inflammatory response in acute pancreatitis.
The present study aims at evaluating the role of protein kinase C (PKC) in the development of acute lung injury, production of inflammatory mediators and expression of adhesion molecules on leukocytes after induction of acute pancreatitis (AP). AP was induced by the intraductal infusion of 5% sodium taurodeoxycholate in the rat. The animals had the PKC inhibitor polymyxin B administered intraperitoneally 30min prior to induction of AP. Levels of protein content, protease activity, cytokines and chemokines in bronchoalveolar lavage fluid (BALF) were assessed 1 and 6h after AP induction. Adhesion molecule expression on leukocytes were measured by flowcytometry. Pretreatment with polymyxin B prevented against acute pancreatitis-induced lung injury and the otherwise occurring increases in TNF-alpha, IL-1beta, MCP-1 and IL-10, as well as against the decreases in IL-2, IFNgamma and TIMP-1, decreased protease activity and down-regulation of CD31, CD54 and CD62L on recruited neutrophils and macrophages in BALF. The results indicate that the leukocyte response in acute pancreatitis vary depending on leukocyte subpopulation. It seems that activation of the PKC signalling pathway may play an important role in pancreatitis-associated lung injury.
Zhao
Xia
X
Departments of Surgery, Lund University Hospital, Clinical Sciences, SE-221 85 Lund, Sweden.
Shi
Changbin
C
Wang
Xiangdong
X
Andersson
Roland
R
D000818:Animals; D016207:Cytokines / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000008:administration & dosage; D005434:Flow Cytometry / Q000379:methods; D007962:Leukocytes / Q000187:drug effects / Q000378:metabolism; D008297:Male; D010183:Pancreatic Ducts / Q000187:drug effects / Q000378:metabolism; D010195:Pancreatitis / Q000139:chemically induced / Q000150:complications* / Q000517:prevention & control; D010447:Peptide Hydrolases / Q000378:metabolism; D011014:Pneumonia / Q000209:etiology* / Q000378:metabolism*; D011113:Polymyxins / Q000008:administration & dosage; D011493:Protein Kinase C / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013657:Taurodeoxycholic Acid; D013997:Time Factors
D016207:Cytokines; D004791:Enzyme Inhibitors; D011113:Polymyxins; D013657:Taurodeoxycholic Acid; D011493:Protein Kinase C; D010447:Peptide Hydrolases