Tissue lipopolysaccharide-binding protein expression in rats after thermal injury: potential role of TNF-alpha.
Recent studies have suggested that levels of lipopolysaccharide-binding protein (LBP) might play a harmful role by up-regulating the host's sensitivity to endotoxin. Our previous studies demonstrated that local endotoxin could up-regulate LBP expression after acute insults, however, the definite molecular mechanisms downstream of endotoxin action remain unclear. This study investigates whether tumor necrosis factor (TNF-alpha) might be responsible for the LBP formation during endogenous endotoxemia postburn. Wistar rats were anesthetized, and a 35% TBSA full-thickness burn was created. Animals were randomly divided into normal control, thermal injury and anti-TNF-alpha mAb treatment group. A significant elevation of plasma endotoxin concentration was observed after acute insults. TNF-alpha levels in plasma also rapidly increased after thermal injury. Meanwhile, LBP mRNA expression markedly increased in liver, lungs, kidneys and intestine postburn. There was no detectable TNF-alpha in the plasma of anti-TNF-alpha mAb treated animals. Treatment with anti-TNF-alpha mAb also resulted in significantly lower concentrations of LBP mRNA in local tissues. Additionally, several organ function parameter levels in plasma significantly decreased in treatment group. These results demonstrated that an increase of plasma TNF-alpha levels caused by burns might be associated with a marked elevation of tissue LBP mRNA expression, which could contribute to the development of multiple organ damage.
Fang
Catherine W H
CW
Department of Microbiology and Immunology, Burns Institute, 304th Hospital, 51 Fu-Cheng Road, Beijing 100037, PR China.
Yao
Yong-Ming
YM
Zhai
Hong-Xia
HX
Yu
Yan
Y
Wu
Ye
Y
Lu
Lian-Rong
LR
Sheng
Zhi-Yong
ZY
Sheng
C Y
CY
D000209:Acute-Phase Proteins; D000818:Animals; D002056:Burns / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism*; D004731:Endotoxins / Q000378:metabolism*; D008297:Male; D008562:Membrane Glycoproteins; D012333:RNA, Messenger / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*; D015854:Up-Regulation; D000099231:Lipopolysaccharide-Binding Protein
D000209:Acute-Phase Proteins; D002352:Carrier Proteins; D004731:Endotoxins; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D000099231:Lipopolysaccharide-Binding Protein