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.
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)-infectedpatients. 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: Cheng J Ma; Lei Ni; Ying Zhang; C L Zhang; Xiao Y Wu; Antwan N Atia; Penny Thayer; Jonathan P Moorman; Zhi Q Yao Journal: Immunology Date: 2010-11-23 Impact factor: 7.397
Authors: Ke Wen; Marli S P Azevedo; Ana Gonzalez; Wei Zhang; Linda J Saif; Guohua Li; Ahmed Yousef; Lijuan Yuan Journal: Vet Immunol Immunopathol Date: 2008-10-31 Impact factor: 2.046
Authors: Amy D Paulino; Kiren Ubhi; Edward Rockenstein; Anthony Adame; Leslie Crews; Scott Letendre; Ronald Ellis; Ian P Everall; Igor Grant; Eliezer Masliah Journal: J Neurovirol Date: 2011-06-10 Impact factor: 2.643
Authors: Feng Qian; Christopher R Bolen; Chunxia Jing; Xiaomei Wang; Wei Zheng; Hongyu Zhao; Erol Fikrig; R Douglas Bruce; Steven H Kleinstein; Ruth R Montgomery Journal: Clin Vaccine Immunol Date: 2012-12-05