Bacterial lipopolysaccharide induces uncoupling protein-2 expression in hepatocytes by a tumor necrosis factor-alpha-dependent mechanism.

Published

Journal Article

The liver is a target for bacterial lipopolysaccharide (LPS) and participates in the metabolic response to endotoxemia. Recently published evidence indicates that LPS increases the expression of mitochondrial uncoupling protein-2 (UCP-2) mRNAs in several tissues, including the liver. Because hepatocytes in the healthy liver do not express UCP-2, LPS was thought to induce UCP-2 in liver macrophages, which express UCP-2 constitutively. However, the present studies of cultured peritoneal macrophages indicate that LPS reduces steady state levels of UCP-2 mRNAs in these cells. In contrast, UCP-2 mRNAs are induced in hepatocytes isolated from LPS treated rats and transfection of these hepatocytes with UCP-2 promoter-reporter constructs demonstrates substantial increases in UCP-2 promoter activity. LPS induction of hepatocyte UCP-2 expression is virtually abolished by prior treatment of rats with neutralizing antibodies to tumor necrosis factor alpha (TNF). Futhermore, TNFalpha treatment induces UCP-2 mRNA accumulation in primary cultures of hepatocytes from healthy rats. Thus, hepatocytes are likely to be important contributors to endotoxin-related increases in liver UCP-2 via a mechanism that involves the LPS-inducible cytokine, TNFalpha.

Full Text

Duke Authors

Cited Authors

  • Cortez-Pinto, H; Yang, SQ; Lin, HZ; Costa, S; Hwang, CS; Lane, MD; Bagby, G; Diehl, AM

Published Date

  • October 9, 1998

Published In

Volume / Issue

  • 251 / 1

Start / End Page

  • 313 - 319

PubMed ID

  • 9790953

Pubmed Central ID

  • 9790953

International Standard Serial Number (ISSN)

  • 0006-291X

Digital Object Identifier (DOI)

  • 10.1006/bbrc.1998.9473

Language

  • eng

Conference Location

  • United States