title: Blocking of monocyte chemoattractant protein-1 (MCP-1) activity attenuates the severity of acute pancreatitis in rats.
abstract: BACKGROUND
  Monocyte chemoattractant protein-1 (MCP-1) has been shown to affect the progression of various inflammatory disorders, including pancreatitis. To investigate the role of MCP-1 in acute pancreatitis and to seek possible therapeutic means, we evaluated the effect of a plasmid expression vector containing a dominant-negative mutant MCP-1 gene (mMCP-1).
  
  
  METHODS
  Two rat models of acute pancreatitis were employed that used either cerulein (for mild pancreatitis) or a mixture of 5% taurocholic acid and trypsin (for severe pancreatitis). At 6 h after induction of acute pancreatitis with or without injection of mMCP-1, serum amylase levels and cytokine levels, as well as morphological evaluation of the pancreas, were determined. Survival rates were also evaluated.
  
  
  RESULTS
  Severe pancreatitis was significantly reduced by mMCP-1 injection. mMCP-1 decreased serum levels of amylase, IL-6, IL-10, and LDH, and improved the survival rate 48 h after disease onset. Histopathological changes of pancreas and lungs were also improved by mMCP-1.
  
  
  CONCLUSIONS
  MCP-1 appears to be involved in the progression of severe forms of acute pancreatitis. Our data suggested that MCP-1 is a candidate as a therapeutic target to treat acute pancreatitis.
authors.affiliation: Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Ishibashi
authors.forename: Haifeng
authors.initials: H
authors.lastname: Zhao
authors.forename: Ken
authors.initials: K
authors.lastname: Kawabe
authors.forename: Takamasa
authors.initials: T
authors.lastname: Oono
authors.forename: Kensuke
authors.initials: K
authors.lastname: Egashira
authors.forename: Koichi
authors.initials: K
authors.lastname: Suzuki
authors.forename: Hajime
authors.initials: H
authors.lastname: Nawata
authors.forename: Ryoichi
authors.initials: R
authors.lastname: Takayanagi
authors.forename: Tetsuhide
authors.initials: T
authors.lastname: Ito
mesh_terms: D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D002108:Ceruletide / Q000633:toxicity; D018932:Chemokine CCL2 / Q000037:antagonists & inhibitors* / Q000097:blood; D016207:Cytokines; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005822:Genetic Vectors / Q000008:administration & dosage*; D007267:Injections; D008297:Male; D010179:Pancreas / Q000187:drug effects / Q000473:pathology; D019283:Pancreatitis, Acute Necrotizing / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy*; D010957:Plasmids; D051381:Rats; D017207:Rats, Sprague-Dawley; D012720:Severity of Illness Index; D016896:Treatment Outcome
chemical_list: C491766:Ccl2 protein, rat; D018932:Chemokine CCL2; D016207:Cytokines; D002108:Ceruletide