Bacterial lipopolysaccharide induces uncoupling protein-2 expression in hepatocytes by a tumor necrosis factor-alpha-dependent mechanism.
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.
Cortez-Pinto
H
H
Department of Medicine, Johns Hopkins University, Baltimore, Maryland, USA.
Yang
S Q
SQ
Lin
H Z
HZ
Costa
S
S
Hwang
C S
CS
Lane
M D
MD
Bagby
G
G
Diehl
A M
AM
D000818:Animals; D015152:Blotting, Northern; D007473:Ion Channels; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D008297:Male; D026901:Membrane Transport Proteins; D051379:Mice; D008820:Mice, Obese; D024101:Mitochondrial Proteins; D014176:Protein Biosynthesis; D012313:RNA / Q000032:analysis; D012333:RNA, Messenger / Q000096:biosynthesis / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*; D014475:Uncoupling Agents / Q000378:metabolism*; D000071246:Uncoupling Protein 2
D007473:Ion Channels; D008070:Lipopolysaccharides; D026901:Membrane Transport Proteins; D024101:Mitochondrial Proteins; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; C000604390:Ucp2 protein, mouse; C000604391:Ucp2 protein, rat; D014475:Uncoupling Agents; D000071246:Uncoupling Protein 2; D012313:RNA