PMID- 18297440 OWN - NLM STAT- MEDLINE DCOM- 20080506 LR - 20220330 IS - 0944-1174 (Print) IS - 0944-1174 (Linking) VI - 43 IP - 1 DP - 2008 TI - Blocking of monocyte chemoattractant protein-1 (MCP-1) activity attenuates the severity of acute pancreatitis in rats. PG - 79-85 LID - 10.1007/s00535-007-2126-9 [doi] AB - 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. FAU - Ishibashi, Toshiaki AU - Ishibashi T AD - Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan. FAU - Zhao, Haifeng AU - Zhao H FAU - Kawabe, Ken AU - Kawabe K FAU - Oono, Takamasa AU - Oono T FAU - Egashira, Kensuke AU - Egashira K FAU - Suzuki, Koichi AU - Suzuki K FAU - Nawata, Hajime AU - Nawata H FAU - Takayanagi, Ryoichi AU - Takayanagi R FAU - Ito, Tetsuhide AU - Ito T LA - eng PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20080224 PL - Japan TA - J Gastroenterol JT - Journal of gastroenterology JID - 9430794 RN - 0 (Ccl2 protein, rat) RN - 0 (Chemokine CCL2) RN - 0 (Cytokines) RN - 888Y08971B (Ceruletide) SB - IM MH - Animals MH - Blotting, Northern MH - Blotting, Western MH - Ceruletide/toxicity MH - Chemokine CCL2/*antagonists & inhibitors/blood MH - Cytokines MH - Disease Models, Animal MH - Enzyme-Linked Immunosorbent Assay MH - Genetic Vectors/*administration & dosage MH - Injections MH - Male MH - Pancreas/drug effects/pathology MH - Pancreatitis, Acute Necrotizing/blood/chemically induced/*drug therapy MH - *Plasmids MH - Rats MH - Rats, Sprague-Dawley MH - Severity of Illness Index MH - Treatment Outcome EDAT- 2008/02/26 09:00 MHDA- 2008/05/07 09:00 CRDT- 2008/02/26 09:00 PHST- 2007/08/20 00:00 [received] PHST- 2007/10/08 00:00 [accepted] PHST- 2008/02/26 09:00 [pubmed] PHST- 2008/05/07 09:00 [medline] PHST- 2008/02/26 09:00 [entrez] AID - 10.1007/s00535-007-2126-9 [doi] PST - ppublish SO - J Gastroenterol. 2008;43(1):79-85. doi: 10.1007/s00535-007-2126-9. Epub 2008 Feb 24.