Differential expression of toll-like receptors 2 and 4 in patients with liver cirrhosis.
OBJECTIVE
Toll-like receptors (TLR) 2 and 4 were shown recently to mediate lipopolysaccharide (LPS)/endotoxin effects in vivo. Absence of clinical features, such as fever and leucocytosis, frequent infections, and up-regulation of anti-inflammatory cytokines suggest systemic differential regulation of LPS effects in patients with chronic endotoxinaemia due to liver cirrhosis.


METHODS
Regulation of TLR2 and TLR4 represents a possible pathway to control LPS-induced immune responses in liver cirrhosis.


METHODS
We compared the expression of TLR2 and TLR4 in peripheral blood mononuclear cells (PBMC) (n = 28) and in liver biopsies (n = 20) of controls and of patients with liver cirrhosis by applying the reverse transcriptase polymerase chain reaction technique. The data were correlated to serum levels of LPS and CD14.


RESULTS
Expression of TLR2 was up-regulated (P < 0.01 to P < 0.05) in the PBMC of patients with high serum endotoxin levels, while TLR4 expression in patients at Child-Pugh stage A was down-regulated, irrespective of the origin (alcoholic or viral) of cirrhosis. A strong and significant correlation between expression of TLR2 and serum LPS (r = 0.638, P < 0.01) and soluble CD14 (r = 0.550, P < 0.05) was observed. Intrahepatic expression of TLR2/4 was not altered significantly in patients with liver cirrhosis.


CONCLUSIONS
Our data indicate LPS-driven regulation of TLR2/4 in patients with liver cirrhosis, suggesting involvement in mechanisms of systemic LPS hyporesponsiveness.
Manigold
Tobias
T
Department of Medicine II (Gastroenterology/Hepatology/Infectious Diseases), University Hospital of Mannheim, Mannheim, Germany.
Böcker
Ulrich
U
Hanck
Christoph
C
Gundt
Jutta
J
Traber
Petra
P
Antoni
Christoph
C
Rossol
Siegbert
S
D029721:Drosophila Proteins; D005260:Female; D006526:Hepatitis C / Q000150:complications; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008070:Lipopolysaccharides / Q000097:blood; D008099:Liver / Q000378:metabolism; D008103:Liver Cirrhosis / Q000097:blood / Q000378:metabolism / Q000821:virology; D008104:Liver Cirrhosis, Alcoholic / Q000097:blood / Q000378:metabolism*; D008297:Male; D008562:Membrane Glycoproteins / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D011956:Receptors, Cell Surface / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D015854:Up-Regulation
D029721:Drosophila Proteins; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; C495342:TLR2 protein, human; C495345:TLR4 protein, human; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors