| Autor: |
Miyako, Murakawa, Yasuhiro, Asahina, Mina, Nakagawa, Naoya, Sakamoto, Sayuri, Nitta, Akiko, Kusano-Kitazume, Takako, Watanabe, Fukiko, Kawai-Kitahata, Satoshi, Otani, Miki, Taniguchi, Fumio, Goto, Yuki, Nishimura-Sakurai, Yasuhiro, Itsui, Seishin, Azuma, Sei, Kakinuma, Mamoru, Watanabe |
| Rok vydání: |
2014 |
| Předmět: |
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| Zdroj: |
Journal of gastroenterology and hepatology. 30(6) |
| ISSN: |
1440-1746 |
| Popis: |
Interferon (IFN) λ plays an important role in innate immunity to protect against hepatitis C viral (HCV) infection. Single nucleotide polymorphisms (SNPs) near IL28B (IFNλ3) are strongly associated with treatment response to IFNα therapy in chronic hepatitis C (CHC) patients. Recently, IFNλ4 related to IL28B-unfavorable allele was discovered. However, the impact of IFNλs on CHC is unknown. We aimed to investigate the mechanism underlying responsiveness to IFN-based therapy in CHC associated with SNPs near IL28B.We evaluated the basal mRNA levels and ex-vivo induction of IFNλ expression including IFNλ4 in peripheral blood mononuclear cells (PBMCs) from 50 CHC patients treated with pegylated-IFNα/RBV. Furthermore, we investigated the effect of IFNλ4 on induction of IL28B in vitro.When PBMCs were stimulated with IFNα and polyinosinic-polycytidylic acid, IL28B induction was significantly lower in patients with IL28B-unfavorable genotype (rs12979860 CT/TT) than those with IL28B-favorable genotype (rs12979860 CC; P=0.049). IL28B induction was lower in nonresponders than in relapsers (P = 0.04), and it was also lower in nonsustained virological responder patients for triple therapy including NS3 protease inhibitors. IFNλ4 mRNA was detected in 12 of 26 patients with IL28B-unfavorable SNP, and IFNλ4 expression was associated with lower IL28B induction in patients with IL28B-unfavorable genotype (P=0.04) and nonresponse to IFNα therapy (P=0.003). Overexpression of IFNλ4 suppressed IL28B induction and promoter activation.Impaired induction of IL28B, related to IFNλ4 expression in PBMCs of IL28B-unfavorable patients, is associated with nonresponse to IFNα-based therapy for hepatitis C viral infection. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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