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Blocking of monocyte chemoattractant protein-1 (MCP-1) activity attenuates the severity of acute pancreatitis in rats

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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.

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Authors and Affiliations

  1. Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan

    Toshiaki Ishibashi, Haifeng Zhao, Ken Kawabe, Takamasa Oono, Hajime Nawata, Ryoichi Takayanagi & Tetsuhide Ito

  2. Cardiovascular Medicine, Graduate School of Medical Science, Kyushu University, Fukuoka, Japan

    Kensuke Egashira

  3. Department of Bioregulation, Leprosy Research Center, National Institute of Infectious Diseases, Tokyo, Japan

    Koichi Suzuki

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  1. Toshiaki Ishibashi
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  2. Haifeng Zhao
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  3. Ken Kawabe
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  4. Takamasa Oono
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  9. Tetsuhide Ito
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Ishibashi, T., Zhao, H., Kawabe, K. et al. Blocking of monocyte chemoattractant protein-1 (MCP-1) activity attenuates the severity of acute pancreatitis in rats. J Gastroenterol 43, 79–85 (2008). https://doi.org/10.1007/s00535-007-2126-9

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  • DOI: https://doi.org/10.1007/s00535-007-2126-9

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