Resistin reinforces interferon λ-3 to eliminate hepatitis C virus with fine-tuning from RETN single-nucleotide polymorphisms
| Autor: | Chen-Ming Hsu, Kung-Hao Liang, Chia-Chi Lo, Cheng-Lung Ku, Ya-Ting Cheng, Ming-Ling Chang, Chau-Ting Yeh, Cheng-Tang Chiu |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
Adult
Male 0301 basic medicine medicine.medical_specialty endocrine system diseases Hepatitis C virus Hepacivirus Single-nucleotide polymorphism medicine.disease_cause Polymorphism Single Nucleotide Peripheral blood mononuclear cell Article 03 medical and health sciences Interferon Internal medicine medicine Humans Resistin Multidisciplinary biology business.industry Interleukins nutritional and metabolic diseases Interleukin Hepatitis C respiratory system medicine.disease biology.organism_classification 030104 developmental biology Endocrinology Immunology Female Interferons business hormones hormone substitutes and hormone antagonists medicine.drug |
| Zdroj: | Scientific Reports |
| ISSN: | 2045-2322 |
| DOI: | 10.1038/srep30799 |
| Popis: | The effect of resistin (RETN) on the response to anti-HCV therapy remains unclear. A prospective cohort study was performed using 655 consecutive HCV patients, of whom 513 had completed a course of interferon-based therapy. Multivariate and GEE analyses revealed four RETN single-nucleotide polymorphisms (SNPs), rs34861192, rs3219175, rs3745367 and rs1423096, to be synergistically associated with resistin levels. After adjusting for co-factors such as interferon λ-3 (IFNL3)-rs12979860, the resistin level and the hyper-resistinemic genotype at the 4 RETN SNPs were positively and negatively associated with a sustained virological response (SVR), respectively. RETN-rs3745367 was in linkage disequilibrium with IFNL3-rs12979860. Compared to non-SVR patients, SVR patients had higher levels of pre-therapy resistin, primarily originating from intrahepatic lymphocytes, stellate cells, Kupffer cells, hepatic progenitor cells and hepatocytes. This difference diminished over the course of therapy, as only SVR patients exhibited a 24-week post-therapy decrease in resistin. Both resistin and IFNL3 mRNAs were upregulated, but only resistin mRNA was upregulated by recombinant resistin in peripheral blood mononuclear cells with and without hyper-resistinemic genotypes of the 4 RETN SNPs, respectively. Fine-tuned by RETN SNPs, intrahepatic, multi-cellular resistin reinforced IFNL3 in eliminating HCV via immunomodulation to counteract pro-inflammation. These results encourage the development of novel resistin-targeted anti-viral agents. |
| Databáze: | OpenAIRE |
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