Dissociation between liver inflammation and hepatocellular damage induced by carbon tetrachloride in myeloid cell-specific signal transducer and activator of transcription 3 gene knockout mice.
Liver injury is associated with inflammation, which is generally believed to accelerate the progression of liver diseases; however, clinical data show that inflammation does not always correlate with hepatocelluar damage in some patients. Investigating the cellular mechanisms underlying these events using an experimental animal model, we show that inflammation may attenuate liver necrosis induced by carbon tetrachloride (CCl(4)) in myeloid-specific signal transducer and activator of transcription 3 (STAT3) knockout mice. As an important anti-inflammatory signal, conditional deletion of STAT3 in myeloid cells results in markedly enhanced liver inflammation after CCl(4) injection. However, these effects are also accompanied by reduced liver necrosis, correlating with elevated serum interleukin-6 (IL-6) and hepatic STAT3 activation. An additional deletion of STAT3 in hepatocytes in myeloid-specific STAT3 knockout mice restored hepatic necrosis but decreased liver inflammation.


CONCLUSIONS
Inflammation-mediated STAT3 activation attenuates hepatocellular injury induced by CCl(4) in myeloid-specific STAT3 knockout mice, suggesting that inflammation associated with a predominance of hepatoprotective cytokines that activate hepatic STAT3 may reduce rather than accelerate hepatocellular damage in patients with chronic liver diseases.
Horiguchi
Norio
N
Section on Liver Biology, Laboratory of Physiologic Studies, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD 20892, USA.
Lafdil
Fouad
F
Miller
Andrew M
AM
Park
Ogyi
O
Wang
Hua
H
Rajesh
Mohanraj
M
Mukhopadhyay
Partha
P
Fu
Xin Yuan
XY
Pacher
Pal
P
Gao
Bin
B
D000818:Animals; D002252:Carbon Tetrachloride Poisoning / Q000473:pathology*; D022781:Hepatocytes / Q000378:metabolism; D007249:Inflammation / Q000139:chemically induced / Q000473:pathology*; D008099:Liver / Q000378:metabolism / Q000473:pathology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009336:Necrosis / Q000139:chemically induced; D018384:Oxidative Stress; D050796:STAT3 Transcription Factor / Q000235:genetics* / Q000502:physiology
D050796:STAT3 Transcription Factor