PMID- 21527401
OWN - NLM
STAT- MEDLINE
DCOM- 20111013
LR  - 20110721
IS  - 1472-4146 (Electronic)
IS  - 0021-9746 (Linking)
VI  - 64
IP  - 8
DP  - 2011 Aug
TI  - Monocyte chemoattractant protein-1 derived from biliary innate immunity 
      contributes to hepatic fibrogenesis.
PG  - 660-5
LID - 10.1136/jclinpath-2011-200040 [doi]
AB  - AIMS: Monocyte chemoattractant protein-1 (MCP-1) is a major chemotactic factor 
      for hepatic stellate cells (HSCs) associated with hepatic fibrosis. In this 
      study, among several fibrogenetic factors derived from biliary epithelial cells 
      (BECs), MCP-1 produced by the biliary innate immune system was found to be most 
      critical in the histogenesis of hepatic fibrogenesis. METHODS: Using cultured 
      human BECs, the expression of five fibrogenetic factors including MCP-1 on 
      stimulation with Toll-like receptor ligands, inflammatory cytokines or bile acids 
      was examined. Moreover, in situ detection of MCP-1 and alpha-smooth muscle actin 
      proteins was performed using sections from normal and diseased livers by 
      immunohistochemistry. RESULTS: All fibrogenetic factors were detected in BECs, 
      but only MCP-1 expression was upregulated, by all the Toll-like receptor ligands, 
      IL-1beta, and tumour necrosis factor-alpha. Proliferating bile ductules in interface 
      areas expressed MCP-1 in diseased livers accompanying alpha-smooth muscle 
      actin-positive activated HSCs. CONCLUSIONS: Bile ductules proliferate in various 
      hepatobiliary diseases, and its significance is still unknown. This study 
      demonstrated that BECs in bile ductules could produce MCP-1, particularly, via 
      biliary innate immunity, suggesting that MCP-1 derived from BECs plays an 
      important role in the recruitment of HSCs to interface areas and the activation 
      of HSCs resulting in the progression of periportal fibrosis.
FAU - Harada, Kenichi
AU  - Harada K
AD  - Department of Human Pathology, Kanazawa University Graduate School of Medicine, 
      Kanazawa, Japan. kenichih@med.kanazawa-u.ac.jp
FAU - Chiba, Mayumi
AU  - Chiba M
FAU - Okamura, Atsushi
AU  - Okamura A
FAU - Hsu, Maylee
AU  - Hsu M
FAU - Sato, Yasunori
AU  - Sato Y
FAU - Igarashi, Saya
AU  - Igarashi S
FAU - Ren, Xiang Shan
AU  - Ren XS
FAU - Ikeda, Hiroko
AU  - Ikeda H
FAU - Ohta, Hajime
AU  - Ohta H
FAU - Kasashima, Satomi
AU  - Kasashima S
FAU - Kawashima, Atsuhiro
AU  - Kawashima A
FAU - Nakanuma, Yasuni
AU  - Nakanuma Y
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110427
PL  - England
TA  - J Clin Pathol
JT  - Journal of clinical pathology
JID - 0376601
RN  - 0 (Bile Acids and Salts)
RN  - 0 (CCR2 protein, human)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Cytokines)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, CCR2)
RN  - 0 (Toll-Like Receptors)
SB  - IM
MH  - Bile Acids and Salts/pharmacology
MH  - Bile Ducts, Intrahepatic/*immunology
MH  - Cells, Cultured
MH  - Chemokine CCL2/biosynthesis/*immunology/metabolism
MH  - Cytokines/pharmacology
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Epithelial Cells/immunology
MH  - Humans
MH  - Immunity, Innate/*immunology
MH  - Immunohistochemistry
MH  - Liver Cirrhosis/*immunology
MH  - RNA, Messenger/metabolism
MH  - Receptors, CCR2/metabolism
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Toll-Like Receptors/physiology
EDAT- 2011/04/30 06:00
MHDA- 2011/10/14 06:00
CRDT- 2011/04/30 06:00
PHST- 2011/04/30 06:00 [entrez]
PHST- 2011/04/30 06:00 [pubmed]
PHST- 2011/10/14 06:00 [medline]
AID - jclinpath-2011-200040 [pii]
AID - 10.1136/jclinpath-2011-200040 [doi]
PST - ppublish
SO  - J Clin Pathol. 2011 Aug;64(8):660-5. doi: 10.1136/jclinpath-2011-200040. Epub 
      2011 Apr 27.