Profile of expression of certain markers of apoptosis in chronic hepatitis C and hepatitis B patients in an Egyptian population

Archives of Virology - Tập 161 - Trang 2369-2378 - 2016
Mahmoud El-Bendary1, Samia Hawas2, Dina El-Hammady1, Al-Hadidy Mohammed Al-Hadidy3, Heba Eldegla2
1Tropical Medicine and Hepatology, Mansoura Faculty of Medicine, Mansoura University, Mansoura, Egypt
2Medical Microbiology and Immunology, Mansoura Faculty of Medicine, Mansoura University, Mansoura, Egypt
3Internal Medicine, Mansoura Faculty of Medicine, Mansoura University, Mansoura, Egypt

Tóm tắt

Increased peripheral blood mononuclear cell (PBMC) apoptosis during viral hepatitis has been suggested to cause impaired regulation of the immune response and maintenance of the infection. The purpose of this work was to study the expression of some apoptotic markers in chronic hepatitis B (CHB) and C (CHC) infections in order to understand the underlying mechanisms of immune failure and viral persistence. This study aims to evaluate the level of PBMC apoptosis and the expression of the apoptosis-related proteins Fas and Bcl-2 in CHB and CHC patients. This case control study was carried out on 38 cases (group I: 20 chronic HCV patients; group II: 18 chronic HBV patients) attending the Tropical Medicine Clinic, Mansoura University Hospital, in addition to 10 healthy controls. Morphological assessment of apoptosis of cultured PBMCs was done. The level of Fas and Bcl-2 expression by PBMCs was detected using flow cytometry. An increased level of apoptosis correlated with increased Fas expression, but no increase in Bcl-2 expression was found on the surface of PBMCs in CHC and CHB patients compared to controls. No significant difference in the level of apoptosis, Fas, or Bcl2 expression between CHC and CHB patients was detected. Modulation of apoptosis, particularly by manipulation of Fas receptor activation, may be of therapeutic benefit in chronic CHB and CHC.

Tài liệu tham khảo

Kiyosawa K, Sodeyama T, Tanaka E, GiboY Yoshizawa K, Nakano Y et al (1990) Interrelationship of blood transfusion, non-A, non-B hepatitis and hepatocellular carcinoma: analysis by detection of antibody to hepatitis C virus. Hepatol 12:671–675 Schmidt J, Blum HE, Thimme R (2013) T-cell responses in hepatitis B and C virus infection: similarities and differences. Emerg Microb Inf 2:1–8 Colombari R, Dhillon AP, Piazzola E et al (1993) Chronic hepatitis in multiple virus infection: histopathological evaluation. Histopathology 22:319–325 Honda M, Kaneko S, Kawai H, Shirota Y, Kobayashi K (2001) Differential gene expression between chronic hepatitis B and C hepatic lesion. Gastroenterology 120:955–966 Honda M, Yamashita T, Ueda T, Takatori H, Nishino R, Kaneko S (2006) Different signaling pathways in the livers of patients with chronic hepatitis B or chronic hepatitis C. Hepatology 44:1122–1138 Koziel MJ (2005) Cellular immune responses against hepatitis C virus. Clin Infect Dis 41:S25–S31 Bertoletti A, Ferrari C (2003) Kinetics of the immune response during HBV and HCV infection. Hepatology 38(1):4–13 Suda T, Nagata S (1994) Purification and characterization of the Fas-Ligand that induces apoptosis. J Exp Med 179(3):873–879 Shresta S, Pham CT, Thomas DA, Graubert TA, Ley TJ (1998) How do cytotoxic lymphocytes kill their targets? Curr Opin Immunol 10:581–587 KagiD Vignaux F, Ledermann B et al (1994) Fas and perforin pathways as major mechanisms of T cell-mediated cytotoxicity. Science 265:528–530 Pham B, Martinot-Peignoux M, Valla D, Dobois S, Degott C, Mosnier JF (2003) Differential expression of perforin and granzyme B in the liver of patients with chronic hepatitis C. Hum Pathol 34:770–777 Schuchmann M, Galle PR (2001) Apoptosis in liver disease. EJGH 13:785–790 Nakamoto Y, Kaneko S, Kobayashi K (2002) Increased susceptibility to apoptosis and attenuated BCL-2 expression in T-lymphocytes and monocytes from patients with advanced chronic hepatitis C. J Leukoc Biol 72:49–55 Woodle ES, Kulkarni S (1998) Programmed cell death, overview. Transplantation 66:681–691 Ogawa S, Sakaguchi K, Takaki A et al (2000) Increase in CD95 (Fas/APO-1) positive CD4+ and CD8+ T-cells in peripheral blood derived from patients with autoimmune hepatitis or chronic hepatitis C with autoimmune phenomena. JGH 15:69–75 GougeonML Montagnier L (1999) Programmed cell death as a mechanism of CD4 and CD8 T cell deletion in AIDS. Molecular control and effect of highly active anti-retroviral therapy. Ann N Y AcadSci 887:199–212 Welsh RM, McNally JM (1999) Immune deficiency, immune silencing, and clonal exhaustion of T cell responses during viral infections. Curr Opin Microbiol 2:382–387 Wold WS, Doronin K, Tot K, Kuppuswamy M, Lichtenstein DL, Tollefson AE (1999) Immune responses to adenoviruses: viral evasion mechanisms and their implications for the clinic. Curr Opin Immunol 11:380–386 Grayson JM, Zajac AJ, AltmanJ D, Ahmed R (2000) Cutting edge: increased expression of Bcl-2 in antigen-specific memory CD8-T cells. J Immunol 164:3950–3954 Feuillard J, Schuhmacher M, Kohanna S, Asso-Bonnet M, Ledeur F, Joubert-Caron R, Bissieres P, Polack A, Bornkamm GW, Raphael M (2000) Inducible loss of NF-kappaB activity is associated with apoptosis and Bcl-2 down-regulation in Epstein-Barr virus-transformed B lymphocytes. Blood 95:2068–2075 World Medical Association (WMA) (2008) Declaration of Helsinki; ethical principles for medical research involving human subjects. 59th WMA General Assembly Seoul McGahon AJ, Martin SJ, BissonetteRP Mahbouli A, Shi Y, Mogil RJ (1995) The end of the cell line: methods for the study of apoptosis in vitro. Methods Cell Biol 46:153–185 Cohen JJ (1993) Overview: mechanisms of apoptosis. Immunol Today 14:126–130 Kumagai M, Coustan-Smith E, Murray L, Silvennoinen O, Murti KG, Evans WE (1995) Ligation of CD38 suppresses human B lymphopoiesis. J Exp Med 181:1101–1110 Hui A, Kulkarni J, Hunter W, McCulloch CA, Cruz TF (1997) Paclitaxel selectively induces mitotic arrest and apoptosis in proliferating bovine synoviocytes. Arthritis Rheum 40:1073–1084 Quackenbush EJ, Letarte J (1995) Identification of several surface proteins of non-T, non-B acute lymphoblastic leukaemia by using monoclonal antibodies. J Immunol 134:1276–1285 Lenard M, Chan KM, Hornung H et al (1999) Mature T-lymphocyte apoptosis-immune regulation in a dynamic and unpredictable antigenic environment. Annu Per Immunol 17:221–253 Roger PM, Breittmayer JP, Dahman M, Bernard A, Dellamonica P, Tran A (2005) Intrahepatic CD4+ T-cell apoptosis is related to METAVIR score in patients with hepatitis-C virus. Scand J Immunol 62:168 Barathan M, Gopal K, Mohamed R et al (2015) Chronic hepatitis C virus infection triggers spontaneous differential expression of biosignatures associated with T-cell exhaustion and apoptosis signaling in peripheral blood mononucleocytes. Apoptosis 20:466–480. doi:10.1007/s10495-014-1084-y Layer GM, Walker BD (2001) Hepatitis C virus infection. NEJM 345:41–52 Bortolami M, Kotsafti A, Cardin R, Farinati F (2008) Fas/FasL system, IL-1bexpression and apoptosis in chronic HBV and HCV liver disease. JVH 15:515–522 Abd El-Latif R, Abd El-Hamid N, Atta A, Basha O (2007) Fas-mediated peripheral T-cell apoptosis in chronic hepatitis-C virus infection. Egypt Med Microbiol 16:243–250 Taya N, Torimotoy M, Shindo M, Hiraik T, Hasebe C, Kohgo Y (2000) Fasmediated apoptosis of peripheral blood mononuclear cells in patients with hepatitis C. Br J Haematol 110:79–89 Lechner F, Wong DK, Dunbar PR et al (2000) Analysis of a successful immune response in persons infected with hepatitis C virus. J Exp Med 91:1499–1512 Toubi E, Kessel A, Goldstein L, Slobodin G, Sabo E, Shmuel Z, Zuckerman E (2001) Enhanced peripheral T-cell apoptosis in chronic hepatitis C virus infection: association with liver disease severity. J Hepatol 35:774–780 Honda M, Kaneko S, Shimazaki T, Matsushita E, Kobayashi K, Ping LH et al (2000) Hepatitis C virus core protein induces apoptosis and impairs cell-cycle regulation. Hepatology 31:1351–1359 Karin M (1998) The NFkB activation pathway: its regulation and role ininflammation and cell survival. Cancer J Sci Am 4:S92–S99 Raghuraman S, Abraham P, Daniel HD, Ramakrishna BS, Sridharan G (2005) Characterization of soluble Fas, Fas ligand and tumour necrosis factoralpha in patients with chronic HCV infection. J Clin Virol 34:63–70 Shehata OH, Farahat NM, Muawia S (2009) expression of apoptotic markers Bcl-2 and Baz in chronic hepatitis C virus patients. Alex Bull 45:85–94 Falcón V, Acosta-Rivero N, Shibayama M, Luna-Munoz J, Miranda-Sanchez M, de la Rosa M, Menéndez I, García W, Gra B, Dueñas-Carrera S, Lopez D, Bravo MG, Fernández-Ortega C, Casillas D, Morales J, Kouri J, Tsutsumi V (2005) Evidences of apoptosis in hepatitis C virus-infected hepatocytes and peripheral blood monocuclear cells in the absence of liver injury. Am J Inf Dis 1:43–49 Nakamura K, Yuh K, Sugyo S, Shijo H, Kimura N, Okumura M (1996) Apoptosis observed in peripheral T lymphocytes from patients with chronic hepatitis B. Gastroenterology 111:156–164 Ji W, Wang HF, Feng CQ (2001) Activation-induced cell death in peripheral blood mononuclear cells (PBMCs) from patients with chronic hepatitis B may be related to abnormal production of interleukin-12 and -10. JVH 8:30–33 Hou CS, Wang GQ, Lu SL, Yue B, Li MR, Wang XY, Yu JW (2004) Role of activation induced cell death in pathogenesis of patients with chronic hepatitis B. WJG 9:2356–2358 Baumann S, Krueger A, Kirchhoff S, Krammer PH (2002) Regulation of T cell apoptosis during the immune responseCurr. Mol Med 2:257–272 Ehrmann J Jr, Galluszkova D, Ehrmann J, Krc I, Jezdinska V, Vojtesck B, Murray PG, Kalao L (2000) Apoptosis-related proteins, Bcl-2, Bax, Fas, FasL, and PCNA in liver biopsies of patients with chronic hepatitis B virus infection. Pathol Oncol Res 6:130–135 Luo KX, Zhu YF, Zhang LX, He HT, Wang XS, Zhang L (1997) In situ investigation of Fas/FasL expression in chronic hepatitis B infection and related liver disease. JVH 4:303–307 Tang DG, Porter AT (1996) Apoptosis: a current molecular analysis. Pathol Oncol Res 2:117–131