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

Norio Horiguchi, Fouad Lafdil, Andrew M. Miller, Ogyi Park, Hua Wang, Mohanraj Rajesh, Partha Mukhopadhyay, Xin Yuan Fu, Pal Pacher, Bin Gao

Research output: Contribution to journalArticle

45 Scopus citations

Abstract

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 (CCl4) 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 CCl4 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. Conclusion: Inflammation-mediated STAT3 activation attenuates hepatocellular injury induced by CCl4 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.

Original languageEnglish (US)
Pages (from-to)1724-1734
Number of pages11
JournalHepatology
Volume51
Issue number5
DOIs
StatePublished - May 1 2010

ASJC Scopus subject areas

  • Hepatology

Fingerprint Dive into the research topics of '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'. Together they form a unique fingerprint.

  • Cite this