PMID- 20921949
OWN - NLM
STAT- MEDLINE
DCOM- 20110104
LR  - 20230216
IS  - 1530-0307 (Electronic)
IS  - 0023-6837 (Linking)
VI  - 90
IP  - 12
DP  - 2010 Dec
TI  - Kupffer cells are associated with apoptosis, inflammation and fibrotic effects in 
      hepatic fibrosis in rats.
PG  - 1805-16
LID - 10.1038/labinvest.2010.123 [doi]
AB  - Hepatocellular apoptosis, hepatic inflammation, and fibrosis are prominent 
      features in chronic liver diseases. However, the linkage among these processes 
      remains mechanistically unclear. In this study, we examined the apoptosis and 
      activation of Kupffer cells (KCs) as well as their pathophysiological involvement 
      in liver fibrosis process. Hepatic fibrosis was induced in rats by 
      dimethylnitrosamine (DMN) or carbon tetrachloride (CCl4) treatment. KCs were 
      isolated from normal rats and incubated with lipopolysaccharide (LPS) or from 
      fibrotic rats. The KCs were stained immunohistochemically with anti-CD68 
      antibody, a biomarker for KC. The level of expression of CD68 was analyzed by 
      western blot and real-time PCR methods. The apoptosis and pathophysiological 
      involvement of KCs in the formation of liver fibrosis were studied using confocal 
      microscopy. The mRNA and protein expression of CD68 were significantly increased 
      in DMN- and CCL4-treated rats. Confocal microscopy analysis showed that 
      CD68-positive KCs, but not alpha-smooth muscle actin (SMA)-positive cells, underwent 
      apoptosis in the liver of DMN- and CCL4-treated rats. It was also revealed that 
      the terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling and 
      CD68-double-positive apoptotic KCs located in the portal or fibrotic septa area 
      were situated next to hepatic stellate cells (HSCs). Tumor necrosis factor-alpha 
      (TNF-alpha) and KC co-localized in the liver in the neighbor of HSCs. The double 
      alpha-SMA- and collagen type I-positive cells predominantly existed in fibrotic 
      septa, and those cells were co-localized clearly with CD68-positive cells. 
      Interestingly, some CD68 and Col (1) double positive, but completely negative for 
      alpha-SMA, were found in the portal areas and hepatic sinusoids; this phenomenon was 
      also validated in primary isolated KCs after 6 h LPS exposure or fibrotic rats in 
      vitro. These results show that KCs are associated with hepatocellular apoptosis, 
      inflammation, and fibrosis process in a liver fibrosis models.
FAU - Liu, Cheng
AU  - Liu C
AD  - Institute of Liver Diseases, Shuguang Hospital, Shanghai, People's Republic of 
      China.
FAU - Tao, Qing
AU  - Tao Q
FAU - Sun, Mingyu
AU  - Sun M
FAU - Wu, Jim Z
AU  - Wu JZ
FAU - Yang, Wengang
AU  - Yang W
FAU - Jian, Ping
AU  - Jian P
FAU - Peng, Jinghua
AU  - Peng J
FAU - Hu, Yiyang
AU  - Hu Y
FAU - Liu, Chenghai
AU  - Liu C
FAU - Liu, Ping
AU  - Liu P
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20101004
PL  - United States
TA  - Lab Invest
JT  - Laboratory investigation; a journal of technical methods and pathology
JID - 0376617
RN  - 0 (Collagen Type I)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - CL2T97X0V0 (Carbon Tetrachloride)
RN  - M43H21IO8R (Dimethylnitrosamine)
SB  - IM
MH  - Animals
MH  - *Apoptosis/drug effects
MH  - Carbon Tetrachloride
MH  - Collagen Type I/metabolism
MH  - Dimethylnitrosamine/pharmacology
MH  - Fibrosis/*pathology
MH  - Hepatic Stellate Cells/cytology/metabolism
MH  - Inflammation/metabolism/*pathology
MH  - Kupffer Cells/*immunology/metabolism/*pathology
MH  - Lipopolysaccharides/pharmacology
MH  - Liver Cirrhosis/chemically induced/metabolism/*pathology
MH  - Male
MH  - Random Allocation
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Tumor Necrosis Factor-alpha/metabolism
EDAT- 2010/10/06 06:00
MHDA- 2011/01/05 06:00
CRDT- 2010/10/06 06:00
PHST- 2010/10/06 06:00 [entrez]
PHST- 2010/10/06 06:00 [pubmed]
PHST- 2011/01/05 06:00 [medline]
AID - S0023-6837(22)02834-3 [pii]
AID - 10.1038/labinvest.2010.123 [doi]
PST - ppublish
SO  - Lab Invest. 2010 Dec;90(12):1805-16. doi: 10.1038/labinvest.2010.123. Epub 2010 
      Oct 4.