Altered expression of TLR homolog RP105 on monocytes hypersensitive to LPS in patients with primary biliary cirrhosis.
OBJECTIVE
Toll-like receptors (TLRs) have emerged as a key component of the innate immune system that triggers antimicrobial responses. Altered monocyte responses to ligands for TLRs have been reported in patients with primary biliary cirrhosis (PBC), yet the precise mechanism remains unknown.


METHODS
We investigated in vitro responses to a TLR4 ligand, lipopolysaccharide (LPS), using peripheral blood mononuclear cells and monocytes from 25 patients with PBC, 10 patients with chronic viral hepatitis (CVH), and 20 healthy individuals.


RESULTS
After stimulation with LPS, we found significantly higher amounts of IL-1beta, IL-6, and IL-8 production in PBC patients. Through the TLR4 signaling pathway, activation of NF-kappaB and expression of MyD88 mRNA were significantly increased in PBC patients, and the level of TLR4 expression was significantly increased on PBC monocytes as compared with CVH patients and controls. Of significance, the surface expression of RP105, which has recently been shown to be involved in negative regulation of TLR4 signaling, on PBC monocytes was significantly decreased in comparison with CVH patients (P=0.016) and controls (P<0.001).


CONCLUSIONS
These results suggest that expression of RP105 and TLR4 is altered on PBC monocytes, which appear to be hypersensitive to LPS, resulting in increased secretion of pro-inflammatory cytokines.
Honda
Yutaka
Y
Division of Gastroenterology and Hepatology, Niigata University Graduate School of Medical and Dental Sciences, 757, Asahimachi-Dori 1, Niigata 951-8510, Japan.
Yamagiwa
Satoshi
S
Matsuda
Yasunobu
Y
Takamura
Masaaki
M
Ichida
Takafumi
T
Aoyagi
Yutaka
Y
D000368:Aged; D015703:Antigens, CD / Q000097:blood* / Q000235:genetics; D002462:Cell Membrane / Q000276:immunology; D002908:Chronic Disease; D005434:Flow Cytometry; D006525:Hepatitis, Viral, Human / Q000097:blood; D006801:Humans; D007136:Immunoglobulins / Q000097:blood; D008024:Ligands; D018950:Lipopolysaccharide Receptors / Q000097:blood; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008105:Liver Cirrhosis, Biliary / Q000097:blood*; D008562:Membrane Glycoproteins / Q000097:blood; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism*; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics; D016328:NF-kappa B / Q000097:blood; D010457:Peptidoglycan / Q000494:pharmacology; D012333:RNA, Messenger / Q000097:blood; D051195:Toll-Like Receptor 2 / Q000097:blood; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D000097802:CD83 Antigen
D015703:Antigens, CD; D007136:Immunoglobulins; D008024:Ligands; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D053594:Myeloid Differentiation Factor 88; D016328:NF-kappa B; D010457:Peptidoglycan; D012333:RNA, Messenger; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D000097802:CD83 Antigen; C092722:CD180 protein, human; C507779:MYD88 protein, human; C495342:TLR2 protein, human