A20 protects mice from D-galactosamine/lipopolysaccharide acute toxic lethal hepatitis.

A20 protects mice from D-galactosamine/lipopolysaccharide acute toxic lethal hepatitis. Research Abstract Details 

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A20 protects mice from D-galactosamine/lipopolysaccharide acute toxic lethal hepatitis. Abstract Text:

Maria B Arvelo,Jeffrey T Cooper,Christopher Longo,Soizic Daniel,Shane T Grey,Jerome Mahiou,Eva Czismadia,Graziella Abu-Jawdeh,Christiane Ferran,

Apoptosis of hepatocytes is a seminal feature of fulminant hepatic failure. We show that the anti-apoptotic protein A20 is upregulated in hepatocytes by pro-inflammatory stimuli and functions to protect from apoptosis and limit inflammation by inhibiting NF-kappaB. Adenoviral mediated hepatic expression of A20 in BALB/c mice yields an 85% survival rate in the D-galactosamine (D-gal)/lipolysaccharide (LPS) model of acute toxic hepatitis compared with 15% to 20 % in control mice. Expression of A20 preserves normal liver function as assessed by prothrombin time. The protective effect of A20 is independent of tumor necrosis factor (TNF) inhibition. Maintaining high circulating TNF levels may be advantageous for liver regeneration. Our data supports this hypothesis as evidenced by increased proliferating cell nuclear antigen (PCNA) expression in the livers of mice expressing A20 compared with a dominant negative mutant of the TNF receptor (TNF-R), 6 hours following D-gal/LPS administration. In conclusion, these results qualify A20 as part of a physiologic, protective response of hepatocytes to injury and a promising gene therapy candidate for clinical applications aimed at preventing and treating viral and toxic fulminant hepatic failure.

A20 protects mice from D-galactosamine/lipopolysaccharide acute toxic lethal hepatitis. Publishing Authors By Initials

MB Arvelo,JT Cooper,C Longo,S Daniel,ST Grey,J Mahiou,E Czismadia,G Abu-Jawdeh,C Ferran,

For similar cells: cells, cultured: tumor cells, cultured research abstracts see: cells: cells, cultured: tumor cells, cultured research

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A20 protects mice from D-galactosamine/lipopolysaccharide acute toxic lethal hepatitis. Journal Published:

PUBLICATION TYPE: Research Support, U.S. Gov't,

Journal: Hepatology (Baltimore, Md.)

VOLUME: 35

Page Numbers: 535-43

Journal Abbreviation: Hepatology

ISSN: 0270-9139

DAY: 9

MONTH: Mar

YEAR: 2002

A20 protects mice from D-galactosamine/lipopolysaccharide acute toxic lethal hepatitis. Information

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LANGUAGE: eng

NlmUniqueID: 8302946

A20 protects mice from D-galactosamine/lipopolysaccharide acute toxic lethal hepatitis. Keywords Mesh Terms:

KEYWORDS: Tumor Cells, Cultured

MESH TERMS: genetics

Chemical & Substance for Abstract: A20 protects mice from D-galactosamine/lipopolysaccharide acute toxic lethal hepatitis. Information

Substance Name: TNFAIP3 protein, human

Registry Number: EC 6.3.2.19

Grant and Affiliation Information for A20 protects mice from D-galactosamine/lipopolysaccharide acute toxic lethal hepatitis.

AFFILIATION: Department of Surgery and Medicine, Immunobiology Research Center, Beth Israel Deaconess Medical Center, Harvard Medical School, 99 Brookline Avenue, Boston, MA 02215, USA.

Country: United States

AGENCY: United States NHLBI

GRANT: R01 HL 57791-01A4

ACRONYM: HL

MEDLINETA: Hepatology

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