Ethanol inhibits the JAK-STAT signaling pathway in freshly isolated rat hepatocytes but not in cultured hepatocytes or HepG2 cells: Evidence for a lack of involvement of ethanol metabolism

Jianping Chen, Dahn L. Clemens, Arthur I. Cederbaum, Bin Gao

Research output: Contribution to journalArticlepeer-review

28 Scopus citations

Abstract

Objectives: To understand the molecular mechanism underlying alcoholic liver injury, effects of acute ethanol on the Janus kinase-signal transducer and activator transcription factor (JAK-STAT) signaling in hepatic cells were studied. Designs and methods: Effects of acute ethanol on the JAK-STAT signaling in freshly isolated, cultured rat hepatocytes, and HepG2 cells were explored. Results: Acute ethanol exposure inhibited IL-6- or IFN-activated STAT in freshly isolated hepatocytes but not in cultured hepatocytes, HepG2 cells, or HepG2 cells transfected with alcohol dehydrogenase (ADH) or cytochrome P450(2E1). The inhibitory action of ethanol in freshly isolated hepatocytes was not antagonized by the ADH inhibitor 4-methylpyrazole (4-MP). Acute exposure of hepatocytes to acetaldehyde or hydrogen peroxide did not suppress STAT activation. Further studies indicated that the loss of response to the inhibitory effect of ethanol was not due to hepatocyte proliferation and collagen contact. Conclusions: Freshly isolated hepatocytes are more susceptible to the inhibitory action of ethanol on the JAK-STAT signaling than cultured hepatocytes or HepG2 cells, which may be implicated in pathogenesis and progression of alcoholic liver disease.

Original languageEnglish
Pages (from-to)203-209
Number of pages7
JournalClinical Biochemistry
Volume34
Issue number3
DOIs
StatePublished - 2001

Keywords

  • 4-Methlepyrazole
  • Acetaldehyde
  • Ethanol
  • Hydrogen peroxide
  • Interferon
  • Interleukin 6
  • Janus kinase-signal transducer and activator transcription factor (JAK-STAT)
  • Liver

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