Lipopolysaccharide suppresses albumin expression by activating NF-kappaB in rat hepatocytes.
BACKGROUND
The severity of hypoalbuminemia has been shown to be related to morbidity and mortality in critical illness, illustrating the need for better understanding of the molecular mechanism of hypoalbuminemia. Lipopolysaccharide(LPS) is a key mediator which induces hypoalbuminemia in sepsis and septic shock. The present studies were performed to identify whether the reduction of albumin expression induced by LPS was mediated by activating nuclear factor kappa B(NF-kappaB) in cultured rat hepatocytes.


METHODS
Primary rat hepatocytes were divided into five groups treated with normal saline or 1 ng/ml, 0.01 microg/ml, 0.1 microg/ml, or 1 microg/ml of LPS for 24 h. The albumin level in the supernatant and NF-kappaB activity in hepatocytes were measured. Hepatocytes were pretreated for 30 min with SN50 (a highly selected inhibitor of NF-kappaB) at different concentrations (10, 30, and 50 microg/ml). After 24 h of treatment with 1 microg/ml of LPS, the culture medium was measured for albumin level. Meanwhile, NF-kappaB activity in hepatocytes was assayed.


RESULTS
LPS dramatically decreased albumin expression and enhanced NF-kappaB activity in rat hepatocytes, especially in the 1 microg/ml LPS group. This reduction in albumin expression induced by LPS can be completely inhibited by SN50 in different concentrations, and the maximal increase in albumin was observed at a SN50 dosage of 30 microg/ml.


CONCLUSIONS
The results suggest that LPS inhibits albumin expression by activating NF-kappaB signaling. NF-kappaB is a critical signaling pathway in LPS-induced hypoalbuminemia which it is worthwhile to understand in studying the molecular mechanism of hypoalbuminemia in sepsis and septic shock.
Wang
Xinying
X
Research Institute of General Surgery, Jinling Hospital, Nanjing, China. wxinying@263.net
Li
Weiqin
W
Lu
Jun
J
Li
Ning
N
Li
Jieshou
J
D000418:Albumins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D022781:Hepatocytes / Q000187:drug effects* / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010455:Peptides / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
D000418:Albumins; D008070:Lipopolysaccharides; D016328:NF-kappa B; D010455:Peptides; C118258:SN50 peptide