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Article

Indoleamine 2,3-dioxygenase expression and activity in patients with hepatitis C virus-induced liver cirrhosis

  • Authors:
    • Kashif Asghar
    • M. Taimour Ashiq
    • Bilal Zulfiqar
    • Amnah Mahroo
    • Kaenat Nasir
    • Sheeba Murad
  • View Affiliations / Copyright

    Affiliations: Molecular immunology Research Group, Atta-ur-Rahman School of Applied Biosciences (ASAB), National University of Sciences & Technology (NUST), Islamabad 44000, Pakistan
  • Pages: 901-904
    |
    Published online on: December 18, 2014
       https://doi.org/10.3892/etm.2014.2146
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Abstract

Indoleamine 2,3‑dioxygenase (IDO) is an immunoregulatory enzyme. It plays a key role in various malignancies, infection and autoimmune diseases. IDO induces immunosuppression through the depletion of tryptophan and its downstream metabolites. Hepatitis C virus (HCV) has infected more than 12 million individuals in Pakistan. The aim of the present study was to assess the expression and activity of IDO in HCV‑infected patients. The functional enzymatic activity of IDO was measured by colorimetric assay. Serum samples from 100 HCV‑infected patients were taken to examine IDO activity and samples from 100 healthy volunteers were used as controls. Liver sections from patients with HCV (n=35) and healthy controls (n=5) were used for immunohistochemical studies. Immunohistochemical analysis revealed that IDO was overexpressed in 28 of 35 (80%) cirrhotic liver samples, whereas 5 of 35 (14.2%) cases presented moderate and 2 of 35 (5.7%) cases presented mild expression of IDO. The enzymatic activity of IDO was significantly higher in the serum samples of HCV‑infected patients as compared with those in the control. These data indicate that the expression of IDO correlated with the pathogenesis of disease. In summary, it is suggested that the high expression of IDO in the progressively cirrhotic livers of HCV‑infected patients might contribute to the development of hepatocellular carcinoma. IDO may characterize a novel therapeutic target against HCV.
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1 

Tan SL, Pause A, Shi Y and Sonenberg N: Hepatitis C therapeutics: current status and emerging strategies. Nat Rev Drug Discov. 1:867–881. 2002. View Article : Google Scholar : PubMed/NCBI

2 

Alter HJ and Seef LB: Recovery, persistence, and sequelae in hepatitis C virus infection: a perspective on long-term outcome. Semin Liver Dis. 20:17–35. 2000. View Article : Google Scholar : PubMed/NCBI

3 

Lauer GM and Walker BD: Hepatitis C virus infection. N Engl J Med. 345:41–52. 2001. View Article : Google Scholar : PubMed/NCBI

4 

El-Serag HB: Hepatocellular carcinoma and hepatitis C in the United States. Hepatology. 36(5 Suppl 1): S74–S83. 2002. View Article : Google Scholar : PubMed/NCBI

5 

Bowen DG and Walker CM: Adaptive immune responses in acute and chronic hepatitis C virus infection. Nature. 436:946–952. 2005. View Article : Google Scholar : PubMed/NCBI

6 

Stone TW and Darlington LG: Endogenous kynurenines as targets for drug discovery and development. Nat Rev Drug Discov. 1:609–620. 2002. View Article : Google Scholar : PubMed/NCBI

7 

Robinson CM, Shirey KA and Carlin JM: Synergistic transcriptional activation of indoleamine dioxygenase by IFG-gamma and tumor necrosis factor-alpha. J Interferon Cytokine Res. 23:413–421. 2003. View Article : Google Scholar : PubMed/NCBI

8 

Abbate I, Romano M, Longo R, et al: Endogenous levels of mRNA for IFNs and IFN-related genes in hepatic biopsies of chronic HCV-infected and non-alcoholic steatohepatitis patients. J Med Virol. 70:581–587. 2003. View Article : Google Scholar : PubMed/NCBI

9 

Grohmann U, Fallarino F and Puccetti P: Tolerance, DCs and tryptophan: much ado about IDO. Trends Immunol. 24:242–248. 2003. View Article : Google Scholar : PubMed/NCBI

10 

Munn DH, Sharma MD and Mellor AL: Ligation of B7-1/B7-2 by human CD4+ T cells trigger indoleamine 2,3-dioxgenase activity in dendritic cells. J Immunol. 172:4100–4110. 2004. View Article : Google Scholar : PubMed/NCBI

11 

Mellor AL and Munn DH: IDO expression by DCs: tolerance and tryptophan catabolism. Nat Rev Immunol. 4:762–774. 2004. View Article : Google Scholar : PubMed/NCBI

12 

Uyttenhove C, Pilotte L, Théate I, et al: Evidence for a tumoral immune resistance mechanism based on tryptophan degradation by indoleamine 2,3-dioxgenase. Nat Med. 9:1269–1274. 2003. View Article : Google Scholar : PubMed/NCBI

13 

Larrea E, Riezu-Boj JI, Gil-Guerrero L, et al: Upregulation of indoleamine 2,3-dioxgenase in hepatitis C virus infection. J Virol. 81:3662–3666. 2007. View Article : Google Scholar : PubMed/NCBI

14 

Sugimoto K, Ikeda F, Stadanlick J, et al: Suppression of HCV-specific T-cells without differential hierarchy demonstrated ex vivo in persistent HCV infection. Hepatology. 38:1437–1448. 2003.PubMed/NCBI

15 

Perrella A, Vitiello L, Atripaldi L, et al: Elevated CD4+/CD25+ T cell frequency and function during acute hepatitis C presage chronic evolution. Gut. 55:1370–1371. 2006. View Article : Google Scholar : PubMed/NCBI

16 

Ulsenheimer A, Gerlach JT, Gruener NH, et al: Detection of functionally altered hepatitis C virus-specific CD4 T cells in acute and chronic hepatitis C. Hepatology. 37:1189–1198. 2003. View Article : Google Scholar : PubMed/NCBI

17 

Cabrera R, Tu Z, Xu Y, et al: An immunomodulatory role for CD4+, CD25+, regulatory T lymphocytes in hepatitis C virus infection. Hepatology. 40:1062–1071. 2004. View Article : Google Scholar : PubMed/NCBI

18 

Boettler T, Spangenberg HC, Neumann-Haefelin C, et al: T cells with a CD4+CD25+ regulatory phenotype suppress in vitro proliferation of virus-specific CD+ T cells during chronic hepatitis C virus infection. J Virol. 79:7860–7867. 2005. View Article : Google Scholar : PubMed/NCBI

19 

Bolacchi F, Sinistro A, Ciaprini C, et al: Increased hepatitis C virus (HCV)-specific CD4+ CD25+ regulatory T lymphocytes and reduced HCV-specific CD4+ T cell response in HCV-infected patients with normal versus abnormal alanine aminotransferase levels. Clin Exp Immunol. 144:188–196. 2006. View Article : Google Scholar : PubMed/NCBI

20 

Ebinuma H, Nakamoto N, Li Y, et al: Identification and in vitro expansion of functional antigen-specific CD25+ FoxP3+ regulatory T-cells in hepatitis C virus infection. J Virol. 82:5043–5053. 2008. View Article : Google Scholar : PubMed/NCBI

21 

Fallarino F, Grohmann U, You S, et al: The combined effects of tryptophan starvation and tryptophan catabolites down-regulate T-cell receptor zeta-chain and induce a regulatory phenotype in naïve T cells. J Immunol. 176:6752–6761. 2006. View Article : Google Scholar : PubMed/NCBI

22 

Hill M, Tanguy-Royer S, Royer P, et al: IDO expands human CD4+CD25 high regulatory T cells by promoting maturation of LPS-treated dendritic cells. Eur J Immunol. 37:3054–3062. 2007. View Article : Google Scholar : PubMed/NCBI

23 

Sharma MD, Baban B, Chandler P, et al: Plasmacytoid dendritic cells from mouse tumor-draining lymph nodes directly activate mature Tregs via indoleamine 2,3-dioxgenase. J Clin Invest. 117:2570–2582. 2007. View Article : Google Scholar : PubMed/NCBI

24 

Terness P, Bauer TM, Röse L, et al: Inhibition of allogenic T cell proliferation by indoleamine 2,3-dioxgenase-expressing dendritic cells: mediation of suppression by tryptophan metabolites. J Exp Med. 447–457. 2002. View Article : Google Scholar

25 

Munn DH and Mellor AL: IDO and tolerance to tumors. Trends Mol Med. 10:15–18. 2004. View Article : Google Scholar : PubMed/NCBI

26 

Takikawa O, Kuroiwa T, Yamazaki F and Kido R: Mechanism of interferon-gamma action. characterization of indoleamine 2,3-dioxygenase in cultured human cells induced by interferon-gamma and evaluation of the enzyme-mediated tryptophan degradation in its anticellular activity. J Biol Chem. 263:2041–2048. 1988.PubMed/NCBI

27 

Grant RS, Naif H, Thuruthyil SJ, et al: Induction of indolamine 2,3-dioxygenase in primary human macrophages by human immunodeficiency virus type 1 is strain dependent. J Virol. 74:4110–4115. 2000. View Article : Google Scholar

28 

Fallarino F, Vacca C, Orabona C, et al: Functional expression of indoleamine 2,3-dioxygenase by murine CD8 alpha+ dendritic cells. Int Immunol. 14:65–68. 2002. View Article : Google Scholar

29 

Grohmann U, Bianchi R, Orabona C, et al: Functional plasticity of dendritic cell subsets as mediated by CD40 versus B7 activation. J Immunol. 171:2581–2587. 2003. View Article : Google Scholar : PubMed/NCBI

30 

Pan K, Wang H, Chen MS, et al: Expression and prognosis role of indoleamine 2,3-dioxygenase in hepatocellular carcinoma. J Cancer Res Clin. 134:1247–1253. 2008. View Article : Google Scholar

31 

Day CL, Lauer GM, Robbins GK, et al: Broad specificity of virus-specific CD4+ T-helper-cell responses in resolved hepatitis C virus infection. J Virol. 76:12584–12595. 2002. View Article : Google Scholar : PubMed/NCBI

32 

Semmo N and Klenerman P: CD4+ T cell responses in hepatitis C virus infection. World J Gastroenterol. 13:4831–4838. 2007.PubMed/NCBI

33 

Chang KM, Thimme R, Melpolder JJ, Oldach D, et al: Differential CD4 (+) and CD8(+) T-cell responsiveness in hepatitis C virus infection. Hepatology. 33:267–276. 2001. View Article : Google Scholar

34 

Perrella A, Vitiello L, Atripaldi L, et al: Elevated CD4+/CD25+ T cell frequency and function during acute hepatitis C presage chronic evolution. Gut. 55:1370–1371. 2006. View Article : Google Scholar : PubMed/NCBI

35 

Ino K, Yoshida N, Kajiyama H, et al: Indoleamine 2,3-dioxygenase is a novel prognostic indicator for dendometrial cancer. Br J Cancer. 95:1555–1561. 2006. View Article : Google Scholar : PubMed/NCBI

36 

Brandacher G, Perathoner A, Ladurner R, et al: Prognostic value of indoleamine 2,3-dioxygenase expression in colorectal cancer: effect on tumor-infiltrating T cells. Clin Cancer Res. 12:1144–1151. 2006. View Article : Google Scholar : PubMed/NCBI

37 

Ishio T, Goto S, Tahara K, et al: Immunoactivative role of indoleamine 2,3-dioxygenase in human hepatocellular carcinoma. J Gastroenterol Hepatol. 19:319–326. 2004. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Asghar K, Ashiq MT, Zulfiqar B, Mahroo A, Nasir K and Murad S: Indoleamine 2,3-dioxygenase expression and activity in patients with hepatitis C virus-induced liver cirrhosis. Exp Ther Med 9: 901-904, 2015.
APA
Asghar, K., Ashiq, M.T., Zulfiqar, B., Mahroo, A., Nasir, K., & Murad, S. (2015). Indoleamine 2,3-dioxygenase expression and activity in patients with hepatitis C virus-induced liver cirrhosis. Experimental and Therapeutic Medicine, 9, 901-904. https://doi.org/10.3892/etm.2014.2146
MLA
Asghar, K., Ashiq, M. T., Zulfiqar, B., Mahroo, A., Nasir, K., Murad, S."Indoleamine 2,3-dioxygenase expression and activity in patients with hepatitis C virus-induced liver cirrhosis". Experimental and Therapeutic Medicine 9.3 (2015): 901-904.
Chicago
Asghar, K., Ashiq, M. T., Zulfiqar, B., Mahroo, A., Nasir, K., Murad, S."Indoleamine 2,3-dioxygenase expression and activity in patients with hepatitis C virus-induced liver cirrhosis". Experimental and Therapeutic Medicine 9, no. 3 (2015): 901-904. https://doi.org/10.3892/etm.2014.2146
Copy and paste a formatted citation
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Spandidos Publications style
Asghar K, Ashiq MT, Zulfiqar B, Mahroo A, Nasir K and Murad S: Indoleamine 2,3-dioxygenase expression and activity in patients with hepatitis C virus-induced liver cirrhosis. Exp Ther Med 9: 901-904, 2015.
APA
Asghar, K., Ashiq, M.T., Zulfiqar, B., Mahroo, A., Nasir, K., & Murad, S. (2015). Indoleamine 2,3-dioxygenase expression and activity in patients with hepatitis C virus-induced liver cirrhosis. Experimental and Therapeutic Medicine, 9, 901-904. https://doi.org/10.3892/etm.2014.2146
MLA
Asghar, K., Ashiq, M. T., Zulfiqar, B., Mahroo, A., Nasir, K., Murad, S."Indoleamine 2,3-dioxygenase expression and activity in patients with hepatitis C virus-induced liver cirrhosis". Experimental and Therapeutic Medicine 9.3 (2015): 901-904.
Chicago
Asghar, K., Ashiq, M. T., Zulfiqar, B., Mahroo, A., Nasir, K., Murad, S."Indoleamine 2,3-dioxygenase expression and activity in patients with hepatitis C virus-induced liver cirrhosis". Experimental and Therapeutic Medicine 9, no. 3 (2015): 901-904. https://doi.org/10.3892/etm.2014.2146
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