title: Expression of Toll-like receptors in chronic hepatitis C virus infection.
abstract: BACKGROUND
  Toll-like receptors (TLRs) are involved in innate immunity. Certain viruses interact with TLRs and mediate antiviral effects as well as immune responses. The aim of this study was to investigate the effect of TLRs on pathogenesis in hepatitis C virus (HCV)-infected patients.
  
  
  METHODS
  Peripheral blood mononuclear cells (PBMC) and CD14+ (monocytes) or CD14- cells from 25 patients with chronic liver disease and 15 healthy subjects were studied for expression of TLRs 2-9 and cytokines of extracted RNA using real-time PCR. Then TLR expression was examined in HepG2 cells transfected with entire or parts (core-NS3, NS3-NS5B) of the HCV open reading frame. TLR expression was calculated as the relative mRNA levels.
  
  
  RESULTS
  Expression of TLRs 4, 7 and 8 in CD14+ cells of PBMC was increased in patients. Levels of tumor necrosis factor (TNF)-alpha, interleukin (IL)-6 and IL-12 p35 for PBMC were also increased in patients. When PBMC were incubated with HCV core protein, enhancement of TLR2 expression and suppression of TLR4 and TLR7 were noted in patients. Similar alteration of TLRs expression was observed in controls. Among HepG2 transfectants, only TLR3 expression was changed; it was suppressed in entire gene transfectant and enhanced in core-NS3 transfectant. Expression of some proteins related to the TLR signaling pathway was suppressed in the entire gene transfectant.
  
  
  CONCLUSIONS
  The results suggest a correlation between expression levels of TLRs and cytokines, and chronic HCV infection. TLR3 recognizes double-stranded RNA and induces type 1 interferon synthesis. Collectively, suppressed expression of TLR3 in cells transfected with entire HCV may be responsible for continuous HCV infection, although a part of the HCV gene enhances its expression.
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Aichi Medical University School of Medicine, Aichi, Japan.
authors.forename: Ken
authors.initials: K
authors.lastname: Sato
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Ishikawa
authors.forename: Akihiko
authors.initials: A
authors.lastname: Okumura
authors.forename: Taeko
authors.initials: T
authors.lastname: Yamauchi
authors.forename: Sayaka
authors.initials: S
authors.lastname: Sato
authors.forename: Minoru
authors.initials: M
authors.lastname: Ayada
authors.forename: Eiji
authors.initials: E
authors.lastname: Matsumoto
authors.forename: Naoki
authors.initials: N
authors.lastname: Hotta
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Oohashi
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Fukuzawa
authors.forename: Shinichi
authors.initials: S
authors.lastname: Kakumu
mesh_terms: D000328:Adult; D000368:Aged; D017209:Apoptosis; D015153:Blotting, Western; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D016207:Cytokines / Q000097:blood; D005260:Female; D019698:Hepatitis C, Chronic / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D012367:RNA, Viral / Q000097:blood; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051193:Toll-Like Receptors / Q000378:metabolism*; D019562:Viral Load
chemical_list: D016207:Cytokines; D012367:RNA, Viral; D051193:Toll-Like Receptors