| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 2794346 | Cytokine | 2013 | 7 Pages |
•IFNL3 (IL28B) genotypes are associated with HCV clearance.•Effects of 3 IFNLs on gene expressions in hepatocytes were examined.•Three IFNLs induced different actions on TLR-related genes.•IFNL3 induces ISGs that are associated with HCV clearance.•Three IFNLs may play different roles in liver diseases.
IFNL1 (IL29), IFNL2 (IL28A) and IFNL3 (IL28B) might play important roles in anti-viral defense. IFNL3 genotypes have been shown to be associated with hepatitis C spontaneous and treatment-induced viral clearance.The effects of IFNL1, IFNL2 and IFNL3 on innate immunity including Toll-like receptor (TLR)-related pathway in human hepatocytes were examined. After G418 screening, we established the human hepatoma stable cell lines HepG2-IL28A, HepG2-IL28B, and HepG2-IL29, expressing IFNL2, IFNL3, and IFNL1 in conditioned medium, respectively, and a control cell line, HepG2-pcDNA3.1. We performed real-time RT-PCR to investigate 84 Toll-like receptor-related gene expressions in triplicate and, using ddCt methods, compared these gene expressions in each cell line.IFNL2, IFNL3 and IFNL1 were respectively detected by ELISA in HepG2-IL28A, HepG2-IL28B and HepG2-IL29. Compared to HepG2-pcDNA3.1 cells, 17 (20.2%), 11 (13.0%) and 16 genes (19.0%) were up-regulated 1.5-fold or more (p < 0.05); 10 (11.9%), 2 (2.3%) and 10 genes (11.9%) were 1.5-fold or more down-regulated (p < 0.05) in HepG2-IL28A, HepG2-IL28B and HepG2-IL29, respectively. EIF2AK2 and SARM1 were up-regulated among all cells. Of interest, TLR3, TLR4 and related molecules CXCL10 (IP10), IL6, EIF2K2, IFNB1, and IRF1, important genes in the progression of HCV-related pathogenesis and antiviral activities against HCV, in HepG2-IL28B, presented different profiles from those of HepG2-IL28A and HepG2-IL29.IFNL3 induces interferon-stimulated genes (ISGs) that are reportedly associated with the progression of HCV-related pathogenesis and antiviral activities against HCV. IFNL is a powerful modulator of innate immune response and it is supposed that the 3 IFNLs may play different roles in the antiviral activity against HBV and HCV.
