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Dowran R, Hosseini S Y, Fattahi M R, Sarvari J. The Effect of Silibinin on the Expression of TLR7, ISG15, and SOCS1 in Peripheral Blood Mononuclear Cells of Hepatitis C Infected Patients in Comparison with Interferon-α. JoMMID 2021; 9 (1) :12-16
URL: http://jommid.pasteur.ac.ir/article-1-279-en.html
The Effect of Silibinin on the Expression of TLR7, ISG15, and SOCS1 in Peripheral Blood Mononuclear Cells of Hepatitis C Infected Patients in Comparison with Interferon-α
Razieh Dowran , Seyed Younes Hosseini , Mohammad Reza Fattahi , Jamal Sarvari
Department of Bacteriology and Virology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.Gastroenterohepatology Research center, Shiraz University of Medical Sciences, Shiraz, Iran
Abstract:   (1576 Views)
Introduction: Silibinin (silibinin A) is the most active silymarin component, which acts both as a hepatoprotective [1] and an antiviral agent. The present study investigated the silibinin effect on IFN-related innate immune genes in PBMCs from HCV-infected patients. Method: 22 chronic HCV patients, including 10 IFN responders and 12 non-responders, were included. Their isolated PBMCs were treated for 6 hours in the presence of silibinin, IFN-α, or their combination. The transcription level of TLR7, ISG15, and SOCS1 genes was compared using real-time PCR. Result: Our result showed that IFN-α induced a significant up-regulation of TLR7 and ISG15 in PBMCs of both responder and non-responder groups. Nevertheless, the SOCS1 gene was not significantly changed in the non-responder group (P=0.32). The combination of IFNα- and silibinin showed a similar pattern to IFN-α alone. By itself, silibinin did not leave a significant change on the expression level of the studied genes. Conclusion: The results indicated that silibinin did not enhance or suppress the expression level of TLR7, ISG15, and SOCS1 genes.  Therefore, it has been suggested that its anti-inflammatory role might be devoid of IFN pathways.
Keywords: HCV, Silibinin, Interferon, ISG15, SOCS1
Full-Text [PDF 1099 kb]   (1150 Downloads)    
Type of Study: Original article | Subject: Infectious diseases and public health
Received: 2020/10/4 | Accepted: 2021/02/28 | Published: 2021/04/27
References
1. Loguercio C, Festi D. Silybin and the liver: from basic research to clinical practice. World J Gastroenterol. 2011; 17 (18): 2288-301. [DOI:10.3748/wjg.v17.i18.2288]
2. Pradat P, Virlogeux V, Trepo E. Epidemiology and Elimination of HCV-Related Liver Disease. Viruses. 2018; 10 (10): 545 [DOI:10.3390/v10100545]
3. Sarvari J, Mansouri M, Hashempoor T, Hosseini SY, Moattari A, Pirbonyeh N, Dowran R, Moayedi J, Musavi Z, Fattahi M-R. Association of genotype and haplotype of IL-28B Gene with Hepatitis C infection outcome in Iran: Spontaneous clearance versus chronic infection. Hepat Mon. 2017; 17 (5): e45745. [DOI:10.5812/hepatmon.45745]
4. Barathan M, Mohamed R, Yong YK, Kannan M, Vadivelu J, Saeidi A, et al. Viral Persistence and Chronicity in Hepatitis C Virus Infection: Role of T-Cell Apoptosis, Senescence and Exhaustion. Cells. 2018; 7 (10): 165. [DOI:10.3390/cells7100165]
5. Sarvari J, Dowran R, Hosseini SY, Fattahi MR, Erfani N. Association of PD-1 gene with outcome of hepatitis C virus infection. EXCLI J. 2018; 24 (17): 935-44.
6. Sarvari J, Moattari A, Pirbonyeh N, Moini M, Hosseini SY. The Impact of IFN-gamma Gene Polymorphisms on Spontaneous Clearance of HCV Infection in Fars Province, Southern of Iran. J Clin Lab Anal. 2016; 30 (4): 301-7. [DOI:10.1002/jcla.21855]
7. Patel M, Rab S, Kalapila AG, Kyle A, Okosun IS, Miller L. Highly Successful Hepatitis C Virus (HCV) Treatment Outcomes in Human Immunodeficiency Virus/HCV-Coinfected Patients at a Large, Urban, Ryan White Clinic. Open Forum Infect Dis. 2017; 4 (2): ofx062. [DOI:10.1093/ofid/ofx062]
8. Ferenci P, Scherzer TM, Kerschner H, Rutter K, Beinhardt S, Hofer H, Schoniger-Hekele M, Holzmann H, Steindl-Munda P. Silibinin is a potent antiviral agent in patients with chronic hepatitis C not responding to pegylated interferon/ribavirin therapy. Gastroenterology. 2008; 135 (5): 1561-7. [DOI:10.1053/j.gastro.2008.07.072]
9. Polyak SJ, Morishima C, Shuhart MC, Wang CC, Liu Y, Lee DY. Inhibition of T-cell inflammatory cytokines, hepatocyte NF-kappaB signaling, and HCV infection by standardized Silymarin. Gastroenterology. 2007; 132 (5): 1925-36. [DOI:10.1053/j.gastro.2007.02.038]
10. Hellerbrand C, Schattenberg JM, Peterburs P, Lechner A, Brignoli R. The potential of silymarin for the treatment of hepatic disorders. Clin Phytoscience. 2016; 2 (1): 7. [DOI:10.1186/s40816-016-0019-2]
11. Lovelace ES, Wagoner J, MacDonald J, Bammler T, Bruckner J, Brownell J, et al. Silymarin Suppresses Cellular Inflammation By Inducing Reparative Stress Signaling. J Nat Prod. 2015; 78 (8): 1990-2000. [DOI:10.1021/acs.jnatprod.5b00288]
12. Giorgi VS, Peracoli MT, Peracoli JC, Witkin SS, Bannwart-Castro CF. Silibinin modulates the NF-kappab pathway and pro-inflammatory cytokine production by mononuclear cells from preeclamptic women. J Reprod Immunol. 2012; 95 (1-2): 67-72. [DOI:10.1016/j.jri.2012.06.004]
13. Liu B, Chen S, Guan Y, Chen L. Type III Interferon Induces Distinct SOCS1 Expression Pattern that Contributes to Delayed but Prolonged Activation of Jak/STAT Signaling Pathway: Implications for Treatment Non-Response in HCV Patients. PLoS One. 2015; 10 (7): e0133800. [DOI:10.1371/journal.pone.0133800]
14. Piganis RA, De Weerd NA, Gould JA, Schindler CW, Mansell A, Nicholson SE, et al. Suppressor of cytokine signaling (SOCS) 1 inhibits type I interferon (IFN) signaling via the interferon alpha receptor (IFNAR1)-associated tyrosine kinase Tyk2. J Biol Chem. 2011; 286 (39): 33811-8. [DOI:10.1074/jbc.M111.270207]
15. Khanlari Z, Sabahi F, Hosseini SY, Ghaderi M. HCV NS3 Blocking Effect on IFN Induced ISGs Like Viperin and IL28 With and Without NS4A. Hepat Mon. 2014; 14 (6): e17822. [DOI:10.5812/hepatmon.17822]
16. Younossi ZM, Baranova A, Afendy A, Collantes R, Stepanova M, Manyam G, et al. Early gene expression profiles of patients with chronic hepatitis C treated with pegylated interferon-alfa and ribavirin. Hepatology. 2009; 49 (3): 763-74. [DOI:10.1002/hep.22729]
17. Dehghan-Manshadi M, Hadinedoushan H, Amirbaigy MK, Zare F, Eslami G, Mirghanizade-Bafghi SA, et al. Relative Expression of Toll-Like Receptors 2 and 7 mRNA in Peripheral Blood of Patients With Hepatitis C. Hepat Mon. 2015; 15 (11): e30427. [DOI:10.5812/hepatmon.30427]
18. Chen L, Li S, McGilvray I. The ISG15/USP18 ubiquitin-like pathway (ISGylation system) in hepatitis C virus infection and resistance to interferon therapy. Int J Biochem Cell Biol. 2011; 43 (10): 1427-31. [DOI:10.1016/j.biocel.2011.06.006]
19. Hashemi SMA, Sarvari J, Fattahi MR, Dowran R, Ramezani A, SY H. Comparison of ISG15, IL28B and USP18 mRNA levels in peripheral blood mononuclear cells of chronic hepatitis B virus infected patients and healthy individuals. Gastroenterol Hepatol Bed Bench. 2019; 12 (1): 38-45.
20. Castellaneta A, Massaro A, Rendina M, D'Errico F, Carparelli S, Rizzi SF, et al. Immunomodulating effects of the anti-viral agent Silibinin in liver transplant patients with HCV recurrence. Transplant Res. 2016; 5: 1. [DOI:10.1186/s13737-016-0030-7]
21. Khodadad M, Hosseini SY, Shenavar F, Erfani N, Bina S, Ahmadian S, et al. Construction of expressing vectors including melanoma differentiation-associated gene-7 (mda-7) fused with the RGD sequences for better tumor targeting. Iran J Basic Med Sci. 2015; 18 (8): 780-7.
22. Dowran R, Sarvari J, Moattari A, Fattahi MR, Ramezani A, Hosseini SY. Analysis of TLR7, SOCS1 and ISG15 immune genes expression in the peripheral blood of responder and non-responder patients with chronic Hepatitis C. Gastroenterol Hepatol Bed Bench. 2017; 10 (4): 272-7.
23. Manns MP, Wedemeyer H, Cornberg M. Treating viral hepatitis C: efficacy, side effects, and complications. Gut. 2006; 55 (9): 1350-9. [DOI:10.1136/gut.2005.076646]
24. Braun DL, Rauch A, Aouri M, Durisch N, Eberhard N, Anagnostopoulos A, et al. A Lead-In with Silibinin Prior to Triple-Therapy Translates into Favorable Treatment Outcomes in Difficult-To-Treat HIV/Hepatitis C Coinfected Patients. PLoS One. 2015; 10 (7): e0133028. [DOI:10.1371/journal.pone.0133028]
25. MacParland SA, Corkum CP, Burgess C, Karwowska S, Kroll W, Michalak TI. Differential expression of interferon alpha inducible genes in peripheral blood mononuclear cells from patients chronically infected with hepatitis C virus and healthy donors. Int Immunopharmacol. 2015; 25 (2): 545-52. [DOI:10.1016/j.intimp.2015.02.037]
26. Esmaeil N, Anaraki SB, Gharagozloo M, Moayedi B. Silymarin impacts on immune system as an immunomodulator: One key for many locks. Int Immunopharmacol. 2017; 50: 194-201. [DOI:10.1016/j.intimp.2017.06.030]
27. Schumann J, Prockl J, Kiemer AK, Vollmar AM, Bang R, Tiegs G. Silibinin protects mice from T cell-dependent liver injury. J Hepatol. 2003; 39 (3): 333-40. [DOI:10.1016/S0168-8278(03)00239-3]
28. Das SK, Mukherjee S. Biochemical and immunological basis of silymarin effect, a milk thistle (Silybum marianum) against ethanol-induced oxidative damage. Toxicol Mech Methods. 2012; 22 (5): 409-13. [DOI:10.3109/15376516.2012.673090]
29. Hou YC, Liou KT, Chern CM, Wang YH, Liao JF, Chang S, et al. Preventive effect of silymarin in cerebral ischemia-reperfusion-induced brain injury in rats possibly through impairing NF-kappaB and STAT-1 activation. Phytomedicine. 2010; 17 (12): 963-73. [DOI:10.1016/j.phymed.2010.03.012]
30. Adeyemo O, Doi H, Rajender Reddy K, Kaplan DE. Impact of oral silymarin on virus- and non-virus-specific T-cell responses in chronic hepatitis C infection. J Viral Hepat. 2013; 20 (7): 453-62. [DOI:10.1111/jvh.12050]
31. Almasi E, Gharagozloo M, Eskandari N, Almasi A, Sabzghabaee AM. Inhibition of Apoptosis and Proliferation in T Cells by Immunosuppressive Silymarine. Iran J Allergy Asthma Immunol. 2017; 16 (2): 107-19.
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This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.