PMID- 15531908
OWN - NLM
STAT- MEDLINE
DCOM- 20050303
LR  - 20230216
IS  - 0023-6837 (Print)
IS  - 0023-6837 (Linking)
VI  - 85
IP  - 1
DP  - 2005 Jan
TI  - Camostat mesilate attenuates pancreatic fibrosis via inhibition of monocytes and 
      pancreatic stellate cells activity.
PG  - 75-89
AB  - Camostat mesilate (CM), an oral protease inhibitor, has been used clinically for 
      the treatment of chronic pancreatitis in Japan. However, the mechanism by which 
      it operates has not been fully understood. Our aim was to evaluate the 
      therapeutic efficacy of CM in the experimental pancreatic fibrosis model induced 
      by dibutyltin dichloride (DBTC), and we also determined the effect of CM on 
      isolated monocytes and panceatic stellate cells (PSCs). In vivo, chronic 
      pancreatitis was induced in male Lewis rats by single administration of 7 mg/kg 
      DBTC and a special diet containing 1 mg/g CM was fed to the DBTC+CM-treated group 
      from day 7, while the DBTC-treated group rats were fed a standard diet. At days 
      0, 7, 14 and 28, the severity of pancreatitis and fibrosis was examined 
      histologically and enzymologically in both groups. In vitro, monocytes were 
      isolated from the spleen of a Lewis rat, and activated with lipopolysaccharide 
      stimulation. Thereafter, the effect of CM on monocyte chemoattractant protein-1 
      (MCP-1) and tumor necrosis factor-alpha (TNF-alpha) production from monocytes was 
      examined. Subsequently, cultured rat PSCs were exposed to CM and tested to see 
      whether their proliferation, MCP-1 production and procollagen alpha1 messenger 
      RNA expression was influenced by CM. In vivo, the oral administration of CM 
      inhibited inflammation, cytokines expression and fibrosis in the pancreas. The in 
      vitro study revealed that CM inhibited both MCP-1 and TNF-alpha production from 
      monocytes, and proliferation and MCP-1 production from PSCs. However, procollagen 
      alpha1 expression in PSCs was not influenced by CM. These results suggest that CM 
      attenuated DBTC-induced rat pancreatic fibrosis via inhibition of monocytes and 
      PSCs activity.
FAU - Gibo, Junya
AU  - Gibo J
AD  - Department of Medicine and Bioregulatory Science, Graduate School of Medical 
      Sciences, Kyushu University, Fukuoka, Japan.
FAU - Ito, Tetsuhide
AU  - Ito T
FAU - Kawabe, Ken
AU  - Kawabe K
FAU - Hisano, Terumasa
AU  - Hisano T
FAU - Inoue, Masanobu
AU  - Inoue M
FAU - Fujimori, Nao
AU  - Fujimori N
FAU - Oono, Takamasa
AU  - Oono T
FAU - Arita, Yoshiyuki
AU  - Arita Y
FAU - Nawata, Hajime
AU  - Nawata H
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Lab Invest
JT  - Laboratory investigation; a journal of technical methods and pathology
JID - 0376617
RN  - 0 (Ccl2 protein, rat)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Esters)
RN  - 0 (Guanidines)
RN  - 0 (Organotin Compounds)
RN  - 0 (Procollagen)
RN  - 0 (Protease Inhibitors)
RN  - 0 (RNA, Messenger)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0FD207WKDU (camostat)
RN  - 4V7M9137X9 (Gabexate)
RN  - J4AQN88R8P (dibutyldichlorotin)
SB  - IM
MH  - Animals
MH  - Cell Proliferation/drug effects
MH  - Chemokine CCL2/genetics/metabolism
MH  - Disease Models, Animal
MH  - Dose-Response Relationship, Drug
MH  - Esters
MH  - Fibrosis/chemically induced/*drug therapy/pathology
MH  - Gabexate/*analogs & derivatives/pharmacology/*therapeutic use
MH  - Guanidines
MH  - Male
MH  - Monocytes/drug effects/metabolism/*pathology
MH  - Organotin Compounds/toxicity
MH  - Pancreas/drug effects/metabolism/*pathology
MH  - Pancreatitis/chemically induced/*drug therapy/pathology
MH  - Procollagen/genetics/metabolism
MH  - Protease Inhibitors/pharmacology/*therapeutic use
MH  - RNA, Messenger/metabolism
MH  - Rats
MH  - Rats, Inbred Lew
MH  - Tumor Necrosis Factor-alpha/genetics/metabolism
EDAT- 2004/11/09 09:00
MHDA- 2005/03/04 09:00
CRDT- 2004/11/09 09:00
PHST- 2004/11/09 09:00 [pubmed]
PHST- 2005/03/04 09:00 [medline]
PHST- 2004/11/09 09:00 [entrez]
AID - S0023-6837(22)01463-5 [pii]
AID - 10.1038/labinvest.3700203 [doi]
PST - ppublish
SO  - Lab Invest. 2005 Jan;85(1):75-89. doi: 10.1038/labinvest.3700203.