Anti-monocyte chemoattractant protein 1 gene therapy attenuates experimental chronic pancreatitis induced by dibutyltin dichloride in rats

H. F. Zhao, Tetsuhide Ito, J. Gibo, Ken Kawabe, takamasa ono, T. Kaku, Y. Arita, Q. W. Zhao, M. Usui, Kensuke Egashira, H. Nawata

研究成果: ジャーナルへの寄稿記事

45 引用 (Scopus)

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Background: Monocyte chemoattractant protein 1 (MCP-1) is a member of the C-C chemokine family and exerts strong chemoattractant activity in monocytes, macrophages, and lymphocytes. Rat pancreatic fibrosis induced by dibulyltin dichloride (DBTC) is considered to be an appropriate chronic pancreatitis model histologically and enzymatically, as has demonstrated in a previous study. Aim: We examined the effect of human dominant negative inhibitor of MCP-1 (mutant MCP-1) on progression of chronic pancreatitis induced by DBTC in a rat model. Methods: We used the experimental model of chronic pancreatitis induced by DBTC in rats. Mutant MCP-1 or empty plasmid at a dose of 50 μg/body weight was administrated into rat thigh muscles on days 4, 11, and 18 after administration of DBTC. On days 14 and 28, we evaluated the effect of mutant MCP-1 morphologically and biochemically. Results: The mutant MCP-1 treated group inhibited early pancreatic inflammation and later pancreatic fibrosis histologically, and showed a decrease in serum MCP-1 concentration, intrapancreatic hydroxyproline, α-smooth muscle actin, and an increase in intrapancreatic amylase and protein content compared with the empty plasmid treated group. The mutant MCP-1 group also inhibited intrapancreatic mRNA expression of cytokines and chemokines. Conclusions: Our findings suggest that monocyte/macrophage recruitment and the systemic MCP-1 signal pathway contribute to progression of chronic pancreatitis, and that blockade of MCP-1 may suppress the development of pancreatic fibrosis.

元の言語英語
ページ(範囲)1759-1767
ページ数9
ジャーナルGut
54
発行部数12
DOI
出版物ステータス出版済み - 12 1 2005

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Chemokine CCL2
Chronic Pancreatitis
Genetic Therapy
Mutant Proteins
Fibrosis
Monocytes
Plasmids
Macrophages
dibutyldichlorotin
CC Chemokines
Hydroxyproline
Chemotactic Factors
Amylases
Thigh
Chemokines
Smooth Muscle
Actins
Blood Proteins
Signal Transduction
Theoretical Models

All Science Journal Classification (ASJC) codes

  • Gastroenterology

これを引用

Anti-monocyte chemoattractant protein 1 gene therapy attenuates experimental chronic pancreatitis induced by dibutyltin dichloride in rats. / Zhao, H. F.; Ito, Tetsuhide; Gibo, J.; Kawabe, Ken; ono, takamasa; Kaku, T.; Arita, Y.; Zhao, Q. W.; Usui, M.; Egashira, Kensuke; Nawata, H.

:: Gut, 巻 54, 番号 12, 01.12.2005, p. 1759-1767.

研究成果: ジャーナルへの寄稿記事

Zhao, HF, Ito, T, Gibo, J, Kawabe, K, ono, T, Kaku, T, Arita, Y, Zhao, QW, Usui, M, Egashira, K & Nawata, H 2005, 'Anti-monocyte chemoattractant protein 1 gene therapy attenuates experimental chronic pancreatitis induced by dibutyltin dichloride in rats', Gut, 巻. 54, 番号 12, pp. 1759-1767. https://doi.org/10.1136/gut.2004.049403
Zhao, H. F. ; Ito, Tetsuhide ; Gibo, J. ; Kawabe, Ken ; ono, takamasa ; Kaku, T. ; Arita, Y. ; Zhao, Q. W. ; Usui, M. ; Egashira, Kensuke ; Nawata, H. / Anti-monocyte chemoattractant protein 1 gene therapy attenuates experimental chronic pancreatitis induced by dibutyltin dichloride in rats. :: Gut. 2005 ; 巻 54, 番号 12. pp. 1759-1767.
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abstract = "Background: Monocyte chemoattractant protein 1 (MCP-1) is a member of the C-C chemokine family and exerts strong chemoattractant activity in monocytes, macrophages, and lymphocytes. Rat pancreatic fibrosis induced by dibulyltin dichloride (DBTC) is considered to be an appropriate chronic pancreatitis model histologically and enzymatically, as has demonstrated in a previous study. Aim: We examined the effect of human dominant negative inhibitor of MCP-1 (mutant MCP-1) on progression of chronic pancreatitis induced by DBTC in a rat model. Methods: We used the experimental model of chronic pancreatitis induced by DBTC in rats. Mutant MCP-1 or empty plasmid at a dose of 50 μg/body weight was administrated into rat thigh muscles on days 4, 11, and 18 after administration of DBTC. On days 14 and 28, we evaluated the effect of mutant MCP-1 morphologically and biochemically. Results: The mutant MCP-1 treated group inhibited early pancreatic inflammation and later pancreatic fibrosis histologically, and showed a decrease in serum MCP-1 concentration, intrapancreatic hydroxyproline, α-smooth muscle actin, and an increase in intrapancreatic amylase and protein content compared with the empty plasmid treated group. The mutant MCP-1 group also inhibited intrapancreatic mRNA expression of cytokines and chemokines. Conclusions: Our findings suggest that monocyte/macrophage recruitment and the systemic MCP-1 signal pathway contribute to progression of chronic pancreatitis, and that blockade of MCP-1 may suppress the development of pancreatic fibrosis.",
author = "Zhao, {H. F.} and Tetsuhide Ito and J. Gibo and Ken Kawabe and takamasa ono and T. Kaku and Y. Arita and Zhao, {Q. W.} and M. Usui and Kensuke Egashira and H. Nawata",
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AU - Zhao, H. F.

AU - Ito, Tetsuhide

AU - Gibo, J.

AU - Kawabe, Ken

AU - ono, takamasa

AU - Kaku, T.

AU - Arita, Y.

AU - Zhao, Q. W.

AU - Usui, M.

AU - Egashira, Kensuke

AU - Nawata, H.

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N2 - Background: Monocyte chemoattractant protein 1 (MCP-1) is a member of the C-C chemokine family and exerts strong chemoattractant activity in monocytes, macrophages, and lymphocytes. Rat pancreatic fibrosis induced by dibulyltin dichloride (DBTC) is considered to be an appropriate chronic pancreatitis model histologically and enzymatically, as has demonstrated in a previous study. Aim: We examined the effect of human dominant negative inhibitor of MCP-1 (mutant MCP-1) on progression of chronic pancreatitis induced by DBTC in a rat model. Methods: We used the experimental model of chronic pancreatitis induced by DBTC in rats. Mutant MCP-1 or empty plasmid at a dose of 50 μg/body weight was administrated into rat thigh muscles on days 4, 11, and 18 after administration of DBTC. On days 14 and 28, we evaluated the effect of mutant MCP-1 morphologically and biochemically. Results: The mutant MCP-1 treated group inhibited early pancreatic inflammation and later pancreatic fibrosis histologically, and showed a decrease in serum MCP-1 concentration, intrapancreatic hydroxyproline, α-smooth muscle actin, and an increase in intrapancreatic amylase and protein content compared with the empty plasmid treated group. The mutant MCP-1 group also inhibited intrapancreatic mRNA expression of cytokines and chemokines. Conclusions: Our findings suggest that monocyte/macrophage recruitment and the systemic MCP-1 signal pathway contribute to progression of chronic pancreatitis, and that blockade of MCP-1 may suppress the development of pancreatic fibrosis.

AB - Background: Monocyte chemoattractant protein 1 (MCP-1) is a member of the C-C chemokine family and exerts strong chemoattractant activity in monocytes, macrophages, and lymphocytes. Rat pancreatic fibrosis induced by dibulyltin dichloride (DBTC) is considered to be an appropriate chronic pancreatitis model histologically and enzymatically, as has demonstrated in a previous study. Aim: We examined the effect of human dominant negative inhibitor of MCP-1 (mutant MCP-1) on progression of chronic pancreatitis induced by DBTC in a rat model. Methods: We used the experimental model of chronic pancreatitis induced by DBTC in rats. Mutant MCP-1 or empty plasmid at a dose of 50 μg/body weight was administrated into rat thigh muscles on days 4, 11, and 18 after administration of DBTC. On days 14 and 28, we evaluated the effect of mutant MCP-1 morphologically and biochemically. Results: The mutant MCP-1 treated group inhibited early pancreatic inflammation and later pancreatic fibrosis histologically, and showed a decrease in serum MCP-1 concentration, intrapancreatic hydroxyproline, α-smooth muscle actin, and an increase in intrapancreatic amylase and protein content compared with the empty plasmid treated group. The mutant MCP-1 group also inhibited intrapancreatic mRNA expression of cytokines and chemokines. Conclusions: Our findings suggest that monocyte/macrophage recruitment and the systemic MCP-1 signal pathway contribute to progression of chronic pancreatitis, and that blockade of MCP-1 may suppress the development of pancreatic fibrosis.

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