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 journalArticle

27 Citations (Scopus)

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 (US)
Pages (from-to)203-209
Number of pages7
JournalClinical Biochemistry
Volume34
Issue number3
DOIs
StatePublished - Jun 26 2001

Fingerprint

Janus Kinases
Hep G2 Cells
Transducers
Metabolism
Rats
Hepatocytes
Cultured Cells
Ethanol
Transcription Factors
Alcohol Dehydrogenase
Liver
Cytochrome P-450 CYP2E1
Alcoholic Liver Diseases
Acetaldehyde
Hydrogen Peroxide
Interleukin-6
Collagen
Chemical activation

Keywords

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

ASJC Scopus subject areas

  • Clinical Biochemistry

Cite this

@article{f8752bb235a04a9481e715aef63d24b3,
title = "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",
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.",
keywords = "4-Methlepyrazole, Acetaldehyde, Ethanol, Hydrogen peroxide, Interferon, Interleukin 6, Janus kinase-signal transducer and activator transcription factor (JAK-STAT), Liver",
author = "Jianping Chen and Clemens, {Dahn L} and Cederbaum, {Arthur I.} and Bin Gao",
year = "2001",
month = "6",
day = "26",
doi = "10.1016/S0009-9120(01)00216-8",
language = "English (US)",
volume = "34",
pages = "203--209",
journal = "Clinical Biochemistry",
issn = "0009-9120",
publisher = "Elsevier Inc.",
number = "3",

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TY - JOUR

T1 - Ethanol inhibits the JAK-STAT signaling pathway in freshly isolated rat hepatocytes but not in cultured hepatocytes or HepG2 cells

T2 - Evidence for a lack of involvement of ethanol metabolism

AU - Chen, Jianping

AU - Clemens, Dahn L

AU - Cederbaum, Arthur I.

AU - Gao, Bin

PY - 2001/6/26

Y1 - 2001/6/26

N2 - 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.

AB - 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.

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KW - Liver

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