期刊论文详细信息
BMC Research Notes
The effects of pegylated interferon-α and ribavirin on liver and serum concentrations of activin-A and follistatin in normal Wistar rat: a preliminary report
Ahmed Mohammed Ashshi1  Adel Galal El-Shemi2  Bassem Refaat1 
[1] Laboratory Medicine Department, Faculty of Applied Medical Sciences, Umm Al-Qura University, Al Abdeyah, Makkah, KSA;Department of Pharmacology, Faculty of Medicine, Assiut University, Assiut, Egypt
关键词: Liver;    Ribavirin;    Pegylated interferon-α;    Follistatin;    Activin-A;   
Others  :  1231670
DOI  :  10.1186/s13104-015-1253-2
 received in 2014-08-14, accepted in 2015-06-18,  发布年份 2015
PDF
【 摘 要 】

Background

Activin-A and follistatin regulate the liver and the immune system.

Aims

To measure the effects of treatment with pegylated-interferon-α (Peg-IFN-α) and ribavirin on the concentrations of mature activin-A and follistatin in serum and liver tissue homogenates in rats.

Methods

A total of 28 male Wistar rats were divided equally into four groups as follow: ‘Control group’ (n = 7), ‘PEG only group’ consisted of those that only received a weekly injection of Peg-IFN-α (6 µg/rat) for 4 weeks, ‘RBV only group’ received ribavirin only (4 mg/rat/day) orally for 35 days and the last group received both Peg-IFN-α and ribavirin ‘PEG & RBV group’. The concentrations of candidate proteins in serum and liver samples were measured using ELISA.

Results

Pegylated-interferon-α decreased activin-A and increased follistatin significantly in serum and liver of ‘PEG only’ and ‘PEG & RBV’ groups compared with the ‘Control’ and ‘RBV only’ groups (P < 0.05). There was no significant difference between the ‘RBV only’ and ‘Control’ groups (P > 0.05) in the concentrations of candidate proteins. A significant positive correlations between serum and liver activin-A (r = 0.727; P = 0.02 × 10 −3 ) and follistatin (r = 0.540; P = 0.01) was also detected.

Conclusion

Pegylated-interferon-α modulates the production of activin-A and follistatin by the liver, which is reflected and can be detected at the serum level. Further studies are needed to explore the role of Peg-IFN-α based therapy on the production of activins and follistatin by the liver and immune cells.

【 授权许可】

   
2015 Refaat et al.

【 预 览 】
附件列表
Files Size Format View
20151110081310603.pdf 1281KB PDF download
Figure2. 56KB Image download
Figure1. 53KB Image download
【 图 表 】

Figure1.

Figure2.

【 参考文献 】
  • [1]Averhoff FM, Glass N, Holtzman D: Global burden of hepatitis C: considerations for healthcare providers in the United States. Clin Infect Dis 2012, 55(Suppl 1):S10-S15.
  • [2]Ghany MG, Strader DB, Thomas DL, Seeff LB: Diagnosis, management, and treatment of hepatitis C: an update. Hepatology 2009, 49:1335-1374.
  • [3]Lee C: Daclatasvir: potential role in hepatitis C. Drug Des Dev Ther 2013, 7:1223-1233.
  • [4]European Association for the Study of the Liver: EASL recommendations on treatment of hepatitis C 2014 J Hepatol 2014, 61:373-395.
  • [5]Afdhal NH, Zeuzem S, Schooley RT, Thomas DL, Ward JW, Litwin AH, et al.: The new paradigm of hepatitis C therapy: integration of oral therapies into best practices. J Viral Hepat 2013, 20:745-760.
  • [6]Chan K, Lai MN, Groessl EJ, Hanchate AD, Wong JB, Clark JA, et al.: Cost effectiveness of direct-acting antiviral therapy for treatment-naive patients with chronic HCV genotype 1 infection in the veterans health administration. Clin Gastroenterol Hepatol 2013, 11:1503-1510.
  • [7]Cure S, Bianic F, Gavart S, Curtis S, Lee S, Dusheiko G: Cost-effectiveness of telaprevir in combination with pegylated interferon alpha and ribavirin in previously untreated chronic hepatitis C genotype 1 patients. J Med Econ 2014, 17:65-76.
  • [8]Farrar JD, Murphy KM: Type I interferons and T helper development. Immunol Today 2000, 21:484-489.
  • [9]Jimenez-Sousa MA, Almansa R, de la Fuente C, Caro-Paton A, Ruiz L, Sanchez-Antolin G, et al.: Increased Th1, Th17 and pro-fibrotic responses in hepatitis C-infected patients are down-regulated after 12 weeks of treatment with pegylated interferon plus ribavirin. Eur Cytokine Netw 2010, 21:84-91.
  • [10]Moser M, Murphy KM: Dendritic cell regulation of TH1-TH2 development. Nat Immunol 2000, 1:199-205.
  • [11]Fallahi P, Ferri C, Ferrari SM, Corrado A, Sansonno D, Antonelli A: Cytokines and HCV-related disorders. Clin Dev Immunol 2012, 2012:468107.
  • [12]Tilg H: New insights into the mechanisms of interferon alfa: an immunoregulatory and anti-inflammatory cytokine. Gastroenterology 1997, 112:1017-1021.
  • [13]Ueyama M, Nakagawa M, Sakamoto N, Onozuka I, Funaoka Y, Watanabe T, et al.: Serum interleukin-6 levels correlate with resistance to treatment of chronic hepatitis C infection with pegylated-interferon-alpha2b plus ribavirin. Antivir Ther 2011, 16:1081-1091.
  • [14]Pavon-Castillero EJ, Munoz-de-Rueda P, Lopez-Segura R, Gila A, Quiles R, Munoz-Gamez JA, et al.: Importance of IL-10 and IL-6 during chronic hepatitis C genotype-1 treatment and their relation with IL28B. Cytokine 2013, 61:595-601.
  • [15]Refaat BA, Bahathiq AO, Sockanathan S, Stewart RL, Wells M, Ledger WL: Production and localization of activins and activin type IIA and IIB receptors by the human endosalpinx. Reproduction 2004, 128:249-255.
  • [16]Rodgarkia-Dara C, Vejda S, Erlach N, Losert A, Bursch W, Berger W, et al.: The activin axis in liver biology and disease. Mutat Res 2006, 613:123-137.
  • [17]Werner S, Alzheimer C: Roles of activin in tissue repair, fibrosis, and inflammatory disease. Cytokine Growth Factor Rev 2006, 17:157-171.
  • [18]Patella S, Phillips DJ, de Kretser DM, Evans LW, Groome NP, Sievert W: Characterization of serum activin-A and follistatin and their relation to virological and histological determinants in chronic viral hepatitis. J Hepatol 2001, 34:576-583.
  • [19]Elsammak MY, Amin GM, Khalil GM, Ragab WS, Abaza MM: Possible contribution of serum activin A and IGF-1 in the development of hepatocellular carcinoma in Egyptian patients suffering from combined hepatitis C virus infection and hepatic schistosomiasis. Clin Biochem 2006, 39:623-629.
  • [20]Refaat B, Ashshi A, El-Shemi A, AlZanbagi A: Effects of chronic hepatitis C genotype 1 and 4 on serum activins and follistatin in treatment naïve patients and their correlations with interleukin-6, tumour necrosis factor-α, viral load and liver damage. Clin Exp Med 2014.
  • [21]Refaat B, El-Shemi AG, Ashshi AM, Alzanbagi A: Serum activins and follistatin during the treatment of chronic hepatitis C genotypes 1 and 4 and their correlations with viral load and liver enzymes: a preliminary report. Gastroenterol Res Pract 2014, 2014:628683.
  • [22]Refaat B, Ashour TH, El-Shemi AG: Ribavirin induced anaemia: the effect of vitamin D supplementation on erythropoietin and erythrocyte indices in normal Wistar rat. Int J Clin Exp Med 2014, 7:2667-2676.
  • [23]Sierra-Filardi E, Puig-Kroger A, Blanco FJ, Nieto C, Bragado R, Palomero MI, et al.: Activin A skews macrophage polarization by promoting a proinflammatory phenotype and inhibiting the acquisition of anti-inflammatory macrophage markers. Blood 2011, 117:5092-5101.
  • [24]Refaat B, Ashshi AM, El-Shemi AG, Azhar E (2015) Activins and follistatin in chronic hepatitis C and its treatment with pegylated-interferon-α based therapy. Mediat Inflamm 2015:Art ID 287640. doi:10.1155/2015/287640
  • [25]Jones KL, de Kretser DM, Patella S, Phillips DJ: Activin A and follistatin in systemic inflammation. Mol Cell Endocrinol 2004, 225:119-125.
  • [26]Jones KL, de Kretser DM, Clarke IJ, Scheerlinck JP, Phillips DJ: Characterisation of the rapid release of activin A following acute lipopolysaccharide challenge in the ewe. J Endocrinol 2004, 182:69-80.
  • [27]Hammond T, Lee S, Watson MW, Flexman JP, Cheng W, Fernandez S, et al.: Toll-like receptor (TLR) expression on CD4+ and CD8+ T-cells in patients chronically infected with hepatitis C virus. Cell Immunol 2010, 264:150-155.
  • [28]Ahlenstiel G, Edlich B, Hogdal LJ, Rotman Y, Noureddin M, Feld JJ et al (2011) Early changes in natural killer cell function indicate virologic response to interferon therapy for hepatitis C. Gastroenterology 141:1231–1239 (1239 e1–2)
  • [29]Semitekolou M, Alissafi T, Aggelakopoulou M, Kourepini E, Kariyawasam HH, Kay AB, et al.: Activin-A induces regulatory T cells that suppress T helper cell immune responses and protect from allergic airway disease. J Exp Med 2009, 206:1769-1785.
  • [30]Famulski KS, Sis B, Billesberger L, Halloran PF: Interferon-gamma and donor MHC class I control alternative macrophage activation and activin expression in rejecting kidney allografts: a shift in the Th1–Th2 paradigm. Am J Transpl 2008, 8:547-556.
  • [31]Pham TN, Lin DM, Mulrooney-Cousins PM, Churchill ND, Kowala-Piaskowska A, Mozer-Lisewska I, et al.: Hepatitis C virus load and expression of a unique subset of cellular genes in circulating lymphoid cells differentiate non-responders from responders to pegylated interferon alpha-ribavirin treatment. J Med Virol 2013, 85:441-448.
  • [32]Refaat B, Amer S, Ola B, Chapman N, Ledger W: The expression of activin-betaA- and -betaB-subunits, follistatin, and activin type II receptors in fallopian tubes bearing an ectopic pregnancy. J Clin Endocrinol Metab 2008, 93:293-299.
  • [33]Blount AL, Vaughan JM, Vale WW, Bilezikjian LM: A Smad-binding element in intron 1 participates in activin-dependent regulation of the follistatin gene. J Biol Chem 2008, 283:7016-7026.
  • [34]Wilson KM, Smith AI, Phillips DJ: Stimulatory effects of lipopolysaccharide on endothelial cell activin and follistatin. Mol Cell Endocrinol 2006, 253:30-35.
  • [35]Abe M, Shintani Y, Eto Y, Harada K, Fujinaka Y, Kosaka M, et al.: Interleukin-1 beta enhances and interferon-gamma suppresses activin A actions by reciprocally regulating activin A and follistatin secretion from bone marrow stromal fibroblasts. Clin Exp Immunol 2001, 126:64-68.
  • [36]Keelan JA, Zhou RL, Evans LW, Groome NP, Mitchell MD: Regulation of activin A, inhibin A, and follistatin production in human amnion and choriodecidual explants by inflammatory mediators. J Soc Gynecol Investig 2000, 7:291-296.
  • [37]Lutchman G, Danehower S, Song BC, Liang TJ, Hoofnagle JH, Thomson M, et al.: Mutation rate of the hepatitis C virus NS5B in patients undergoing treatment with ribavirin monotherapy. Gastroenterology 2007, 132:1757-1766.
  • [38]Stevenson NJ, Murphy AG, Bourke NM, Keogh CA, Hegarty JE, O’Farrelly C: Ribavirin enhances IFN-alpha signalling and MxA expression: a novel immune modulation mechanism during treatment of HCV. PLoS One 2011, 6:e27866.
  • [39]Schneyer AL, Hall HA, Lambert-Messerlian G, Wang QF, Sluss P, Crowley WF Jr: Follistatin-activin complexes in human serum and follicular fluid differ immunologically and biochemically. Endocrinology 1996, 137:240-247.
  • [40]Nakamura T, Sugino K, Titani K, Sugino H: Follistatin, an activin-binding protein, associates with heparan sulfate chains of proteoglycans on follicular granulosa cells. J Biol Chem 1991, 266:19432-19437.
  文献评价指标  
  下载次数:34次 浏览次数:12次