Differential expression of toll-like receptor mRNA in treatment non-responders and sustained virologic responders at baseline in patients with chronic hepatitis C
Article first published online: 21 SEP 2006
Volume 26, Issue 9, pages 1100–1110, November 2006
How to Cite
He, Q., Graham, C. S., Mangoni, E. D. and Koziel, M. J. (2006), Differential expression of toll-like receptor mRNA in treatment non-responders and sustained virologic responders at baseline in patients with chronic hepatitis C. Liver International, 26: 1100–1110. doi: 10.1111/j.1478-3231.2006.01357.x
- Issue published online: 10 OCT 2006
- Article first published online: 21 SEP 2006
- Received 13 March 2006,accepted 31 July 2006
- hepatitis C virus;
- nuclear factor of activated T cells;
- sustained virologic response;
- T-helper (Th)1/2 cytokines;
- toll-like receptors
Abstract: Background/Aims: The contribution of the host immune response to sustained virologic response is not clear in patients with chronic hepatitis C (CHC). The aim of this study was to explore the relationship of the toll-like receptor (TLR) expression with the outcome of antiviral therapy in hepatitis C viral infection.
Methods: Peripheral blood mononuclear cells (PBMC) were obtained from 15 CHC patients before a 48-week treatment with pegylated interferon (PEG IFN) α-2a and ribavirin. A multiplex semi-quantitative reverse-trancriptase polymerase chain reaction (RT-PCR) was used to compare the relative abundance of TLR2–9 transcripts.
Results: mRNA levels of TLR2, 3 and 6 were significantly higher in CHC subjects compared with normal controls (n=8). When patients were classified into non-responders (n=8) and sustained virological responders (n=7) according to the virological outcome of the treatment, there was a clear difference in baseline mRNA expression of TLRs and T-helper (Th) 1/2 cytokines. In addition, the mRNA expression of IFN-γ and nuclear factor of activated T cells (NFAT), which is exclusively expressed in activated T cells, was inversely correlated with that of TLR4, 6 and 9 in non-responders.
Conclusions: TLRs mRNA levels are differentially expressed in baseline PBMC of chronic HCV-infected subjects with or without responsiveness to antiviral therapy.