Expression of Toll-like receptor 4 in various organs in rats with D-galactosamine-induced acute hepatic failure.
OBJECTIVE
Activation of the pro-inflammatory cytokine cascade, including tumor necrosis factor alpha (TNF-alpha) is considered to play an important role in the pathophysiology and clinical outcome of severe liver injury. Kupffer cells, resident macrophages of the liver, have a transmembrane protein Toll-like receptor 4 (TLR4), which recognizes endotoxin (lipopolysaccharide; LPS) or LPS-CD14 complex and mediates macrophage activation and pro-inflammatory cytokine release. D-Galactosamine (GalN), a hepatocyte-specific inhibitor of RNA synthesis, is known to sensitize animals to the lethal effects of LPS and TNF-alpha. In the present study we seek to address TLR4-signaling in the development of GalN-induced acute hepatic failure (AHF) and explore the expression of TLR4 mRNA as compared to TNF-alpha mRNA and CD14 mRNA in the liver, spleen and lung of rats with GalN-induced hepatitis.


METHODS
AHF was induced in male Wistar rats by the intraperitoneal injection of 1 g/kg bodyweight GalN. Expression levels of TNF-alpha, TLR4 and CD14 mRNA in the whole liver, spleen and lung of rats were detected by reverse transcription-polymerase chain reaction analysis.


RESULTS
Expression level of TLR4 mRNA in the liver of rats with GalN-induced AHF was increased parallel with that of TNF-alpha and CD14 mRNA as compared to the control rats. However, expression levels of TNF-alpha, TLR4 and CD14 mRNA in the whole spleen and lung were not different between rats with AHF and control.


CONCLUSIONS
There may be a difference of stimulatory effects of endotoxin on the innate immunity between the liver and other organs of rats with GalN-induced AHF.
Kitazawa
Toshiyuki
T
Third Department of Internal Medicine, Nara Medical University, Kashihara, Nara, Japan.
Tsujimoto
Tatsuhiro
T
Kawaratani
Hideto
H
Fujimoto
Masao
M
Fukui
Hiroshi
H
D000818:Animals; D004195:Disease Models, Animal; D004731:Endotoxins / Q000009:adverse effects; D005688:Galactosamine / Q000009:adverse effects; D007113:Immunity, Innate; D018950:Lipopolysaccharide Receptors / Q000096:biosynthesis; D008099:Liver / Q000187:drug effects; D017114:Liver Failure, Acute / Q000139:chemically induced / Q000276:immunology* / Q000503:physiopathology; D008168:Lung / Q000187:drug effects; D008297:Male; D012333:RNA, Messenger; D051381:Rats; D017208:Rats, Wistar; D013154:Spleen / Q000187:drug effects; D051197:Toll-Like Receptor 4 / Q000096:biosynthesis*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D004731:Endotoxins; D018950:Lipopolysaccharide Receptors; D012333:RNA, Messenger; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; D005688:Galactosamine