Additive activation of hepatic NF-kappaB by ethanol and hepatitis B protein X (HBX) or HCV core protein

involvement of TNF-alpha receptor 1-independent and -dependent mechanisms.

W. H. Kim, F. Hong, B. Jaruga, Z. Hu, S. Fan, T. J. Liang, B. Gao

Research output: Contribution to journalArticle

Abstract

Alcohol consumption and viral hepatitis infection synergistically accelerate liver injury, but the underlying mechanism is not fully understood. Here we have examined the effects of ethanol on hepatitis B protein X (HBX)- or hepatitis C core protein (HCV core protein)-mediated activation of NF-kappaB, a critical signal in hepatic injury, regeneration, and tumor transformation. Acute ethanol or acetaldehyde exposure potentiates HBX or HCV core protein activation of NF-kappaB in primary mouse hepatocytes. Such potentiation can be abolished by blocking ethanol metabolism or overexpression of dominant negative NF-kappaB-inducing kinase (NIK), IkappaB kinase (IKK), or IkappaB. Moreover, pertussis toxin attenuates NF-kappaB activation induced by acetaldehyde but not by HBX or HCV core protein, whereas HBX or HCV core protein-mediated activation of NF-kappaB is abolished completely in tumor necrosis factor a receptor 1 (TNFR1) (-/-) hepatocytes. Finally, chronic ethanol consumption induces hepatic CYP2E1 protein expression and potentiates HBX or HCV core protein activation of NF-kappaB in the liver. These findings suggest that ethanol activates hepatic NF-kappaB via its metabolism and that HBX or HCV core protein activates hepatic NF-kappaB via TNFR1. With the essential role of TNFR1 in alcoholic liver injury, targeting TNFR1 by hepatitis viral proteins could contribute to cooperative effects of alcohol consumption and viral hepatitis on liver disease.

Original languageEnglish (US)
Pages (from-to)2551-2553
Number of pages3
JournalFASEB Journal
Volume15
Issue number13
StatePublished - 2001
Externally publishedYes

Fingerprint

NF-kappa B
Tumor Necrosis Factor Receptors
Hepatitis B
Ethanol
Tumor Necrosis Factor-alpha
Chemical activation
Liver
Proteins
Hepatitis
Acetaldehyde
Metabolism
Alcohol Drinking
Hepatocytes
Wounds and Injuries
I-kappa B Kinase
Alcohols
Cytochrome P-450 CYP2E1
Pertussis Toxin
Viral Proteins
Virus Diseases

Cite this

Additive activation of hepatic NF-kappaB by ethanol and hepatitis B protein X (HBX) or HCV core protein : involvement of TNF-alpha receptor 1-independent and -dependent mechanisms. / Kim, W. H.; Hong, F.; Jaruga, B.; Hu, Z.; Fan, S.; Liang, T. J.; Gao, B.

In: FASEB Journal, Vol. 15, No. 13, 2001, p. 2551-2553.

Research output: Contribution to journalArticle

@article{ca42dad3fa994443bf92d2363126fe68,
title = "Additive activation of hepatic NF-kappaB by ethanol and hepatitis B protein X (HBX) or HCV core protein: involvement of TNF-alpha receptor 1-independent and -dependent mechanisms.",
abstract = "Alcohol consumption and viral hepatitis infection synergistically accelerate liver injury, but the underlying mechanism is not fully understood. Here we have examined the effects of ethanol on hepatitis B protein X (HBX)- or hepatitis C core protein (HCV core protein)-mediated activation of NF-kappaB, a critical signal in hepatic injury, regeneration, and tumor transformation. Acute ethanol or acetaldehyde exposure potentiates HBX or HCV core protein activation of NF-kappaB in primary mouse hepatocytes. Such potentiation can be abolished by blocking ethanol metabolism or overexpression of dominant negative NF-kappaB-inducing kinase (NIK), IkappaB kinase (IKK), or IkappaB. Moreover, pertussis toxin attenuates NF-kappaB activation induced by acetaldehyde but not by HBX or HCV core protein, whereas HBX or HCV core protein-mediated activation of NF-kappaB is abolished completely in tumor necrosis factor a receptor 1 (TNFR1) (-/-) hepatocytes. Finally, chronic ethanol consumption induces hepatic CYP2E1 protein expression and potentiates HBX or HCV core protein activation of NF-kappaB in the liver. These findings suggest that ethanol activates hepatic NF-kappaB via its metabolism and that HBX or HCV core protein activates hepatic NF-kappaB via TNFR1. With the essential role of TNFR1 in alcoholic liver injury, targeting TNFR1 by hepatitis viral proteins could contribute to cooperative effects of alcohol consumption and viral hepatitis on liver disease.",
author = "Kim, {W. H.} and F. Hong and B. Jaruga and Z. Hu and S. Fan and Liang, {T. J.} and B. Gao",
year = "2001",
language = "English (US)",
volume = "15",
pages = "2551--2553",
journal = "FASEB Journal",
issn = "0892-6638",
publisher = "FASEB",
number = "13",

}

TY - JOUR

T1 - Additive activation of hepatic NF-kappaB by ethanol and hepatitis B protein X (HBX) or HCV core protein

T2 - involvement of TNF-alpha receptor 1-independent and -dependent mechanisms.

AU - Kim, W. H.

AU - Hong, F.

AU - Jaruga, B.

AU - Hu, Z.

AU - Fan, S.

AU - Liang, T. J.

AU - Gao, B.

PY - 2001

Y1 - 2001

N2 - Alcohol consumption and viral hepatitis infection synergistically accelerate liver injury, but the underlying mechanism is not fully understood. Here we have examined the effects of ethanol on hepatitis B protein X (HBX)- or hepatitis C core protein (HCV core protein)-mediated activation of NF-kappaB, a critical signal in hepatic injury, regeneration, and tumor transformation. Acute ethanol or acetaldehyde exposure potentiates HBX or HCV core protein activation of NF-kappaB in primary mouse hepatocytes. Such potentiation can be abolished by blocking ethanol metabolism or overexpression of dominant negative NF-kappaB-inducing kinase (NIK), IkappaB kinase (IKK), or IkappaB. Moreover, pertussis toxin attenuates NF-kappaB activation induced by acetaldehyde but not by HBX or HCV core protein, whereas HBX or HCV core protein-mediated activation of NF-kappaB is abolished completely in tumor necrosis factor a receptor 1 (TNFR1) (-/-) hepatocytes. Finally, chronic ethanol consumption induces hepatic CYP2E1 protein expression and potentiates HBX or HCV core protein activation of NF-kappaB in the liver. These findings suggest that ethanol activates hepatic NF-kappaB via its metabolism and that HBX or HCV core protein activates hepatic NF-kappaB via TNFR1. With the essential role of TNFR1 in alcoholic liver injury, targeting TNFR1 by hepatitis viral proteins could contribute to cooperative effects of alcohol consumption and viral hepatitis on liver disease.

AB - Alcohol consumption and viral hepatitis infection synergistically accelerate liver injury, but the underlying mechanism is not fully understood. Here we have examined the effects of ethanol on hepatitis B protein X (HBX)- or hepatitis C core protein (HCV core protein)-mediated activation of NF-kappaB, a critical signal in hepatic injury, regeneration, and tumor transformation. Acute ethanol or acetaldehyde exposure potentiates HBX or HCV core protein activation of NF-kappaB in primary mouse hepatocytes. Such potentiation can be abolished by blocking ethanol metabolism or overexpression of dominant negative NF-kappaB-inducing kinase (NIK), IkappaB kinase (IKK), or IkappaB. Moreover, pertussis toxin attenuates NF-kappaB activation induced by acetaldehyde but not by HBX or HCV core protein, whereas HBX or HCV core protein-mediated activation of NF-kappaB is abolished completely in tumor necrosis factor a receptor 1 (TNFR1) (-/-) hepatocytes. Finally, chronic ethanol consumption induces hepatic CYP2E1 protein expression and potentiates HBX or HCV core protein activation of NF-kappaB in the liver. These findings suggest that ethanol activates hepatic NF-kappaB via its metabolism and that HBX or HCV core protein activates hepatic NF-kappaB via TNFR1. With the essential role of TNFR1 in alcoholic liver injury, targeting TNFR1 by hepatitis viral proteins could contribute to cooperative effects of alcohol consumption and viral hepatitis on liver disease.

UR - http://www.scopus.com/inward/record.url?scp=0035515221&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0035515221&partnerID=8YFLogxK

M3 - Article

VL - 15

SP - 2551

EP - 2553

JO - FASEB Journal

JF - FASEB Journal

SN - 0892-6638

IS - 13

ER -