Altered of apoptotic markers of both extrinsic and intrinsic pathways induced by hepatitis C virus infection in peripheral blood mononuclear cells

Albertoni, Guilherme; Arnoni, Carine Prisco; Latini, Flávia Roche Moreira; Andrade, Sheila Siqueira; Araújo, Pedro Henrique de; Rodrigues, Flaviane Kesia; Rozenchan, Patrícia Bortman; Mendes-Corrêa, Maria Cássia; Leite, Olavo Henrique Munhoz; Schor, Nestor; Girão, M. J. B. C.; Barreto, José Augusto

doi:10.1186/1743-422x-9-314

Cited by 12 publications

(13 citation statements)

References 44 publications

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“…These observations were consistent with other studies (1,16,24). Upon starvation, monocytes and T lymphocytes from chronic HCV + patients and HCV + patients with liver cirrhosis or hepatocellular carcinoma have been reported to display higher death rates than controls (16).…”

Section: Discussionsupporting

confidence: 82%

“…Apoptosis is triggered either by cell surface death receptors (extrinsic pathway) or by disruption of the mitochondrial membrane potential (intrinsic pathway). During apoptosis, downstream effector caspases 3, 6, and 7 are activated, resulting in nuclear poly (ADP-ribose) polymerase cleavage, DNA fragmentation, and cell death (1). Several studies have demonstrated a role for PCD in HCV pathogenesis during liver inflammation and fibrosis, or its progression to hepatocellular carcinoma (6,8,10,18).…”

mentioning

confidence: 99%

“…Programmed cell death (PCD) through apoptosis plays a key role in the maintenance of cellular homeostasis; dysregulation of apoptotic processes may lead to malignancies and/ or immune dysfunction (1). Apoptosis is triggered either by cell surface death receptors (extrinsic pathway) or by disruption of the mitochondrial membrane potential (intrinsic pathway).…”

mentioning

confidence: 99%

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Increased Spontaneous Programmed Cell Death Is Associated with Impaired Cytokine Secretion in Peripheral Blood Mononuclear Cells from Hepatitis C Virus-Positive Patients

et al. 2017

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Peripheral blood mononuclear cells (PBMCs) play a critical role in clearing hepatitis C virus (HCV). PBMC defects have been linked with HCV infection; however, the underlying mechanisms remain obscure. We hypothesized that PBMCs of HCV-infected patients are more susceptible to programmed cell death (PCD), and are therefore unable to clear HCV. We compared spontaneous PBMC PCD and cytokine [interleukin (IL)-1, -6, -8, -10, and -12] secretion between untreated (naive) HCV + and treated [sustained responder (SR)] patients with HCV, and HCV -healthy controls. Spontaneous PBMC PCD was assessed by annexin-V fluorescein isothiocyanate/propidium iodide staining, and cytokine levels were measured by cytometric bead array. Differences between groups were analyzed through paired and nonpaired t tests and Mann-Whitney U test. The rate of spontaneous PCD was higher in PBMCs of naive HCV + patients ( p < 0.0001) and SR-HCV patients ( p < 0.002) than in HCV -controls. Significantly low levels of IL-8, -6, and -10 were detected in the supernatant of cell cultures of PBMCs from naive HCV + ( p < 0.05) and SR-HCV ( p < 0.05) patients relative to HCV -controls. There was no difference between the naive HCV + and SR-HCV groups in terms of PBMC PCD rate or cytokine levels. The present findings indicate that HCV infection is associated with increased PBMC susceptibility to PCD and decreased production of IL-8, -6, and -10.

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Section: Discussionsupporting

confidence: 82%

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confidence: 99%

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Increased Spontaneous Programmed Cell Death Is Associated with Impaired Cytokine Secretion in Peripheral Blood Mononuclear Cells from Hepatitis C Virus-Positive Patients

et al. 2017

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“…Significantly increased expression of Fas receptor in PBMCs were demonstrated in hepatitis C patients with fibrosis and absent necroinflammation [29], suggesting that Fas receptor expression may represent a self-limiting mechanism of the immune response [30], while in hepatitis C patients with cirrhosis and intense necroinflammation, a decrease in Fas expression in PBMC's was observed [29]. However, other studies showed that Fas was similarly expressed on activated T cells of HCV patients compared with that of healthy individuals [26].…”

Section: Discussionmentioning

confidence: 91%

Expression of Fas (CD95) and Bcl-2 in peripheral blood mononuclear cells in patients with chronic HCV and schistosomiasis

El-Bendary

Hawas

Elhammady

et al. 2014

Egyptian Journal of Basic and Applied Sciences

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Schistosomiasis Apoptosis Fas Bcl-2 a b s t r a c t A high incidence of viral persistence and progression to chronic hepatitis are characteristic features of HCV infection. The aim of this case control study was to investigate the expression of the apoptosis related proteins Fas (CD95) and Bcl-2 in peripheral blood mononuclear cells (PBMCs) from patients with chronic HCV and schistosomiasis, and to evaluate their contribution in the development and maintenance of the different clinical forms of these diseases. The level of Fas and Bcl-2 expression in PBMCs was detected using flow cytometry in 85 cases in this study, including chronic HCV (40 patients) and schistosomiasis (25 patients) in addition to 20 healthy controls. Results showed that the increased apoptotic level correlated with increased Fas expression on the surface of PBMCs in chronic HCV patients (p ¼ 0.001) which did not show increased expression of the antiapoptotic factor Bcl-2 (p ¼ 0. 19). Apoptotic PBMCs in intestinal schistosomiasis patientsshowed increased expression of Fas (p ¼ 0.001) but again did not exhibit a difference in Bcl-2 expression (p ¼ 0.61) when compared to either hepatoplenic schistosomiasis or control patients. The Fas expression was highly significant in HCV > schistosomiasis > control (p < 0.002) while non-significant difference was found between the 3 groups as regards to Bcl-2 expression (p > 0.12). It was concluded that the detection of apoptosis of PBMCs in patients with chronic HCV was associated with increased expression of apoptotic markers in comparison with schistosomiasis patients, which may be an indicator of disease progression and severity. Modulation of this process may offer valuable methods of HCV therapy.

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“…Both in vitro studies and in vivo models have demonstrated the ability of HCV to induce apoptosis [4][5][6][7]. Furthermore, some studies including adult patients indicated that hepatocyte apoptosis plays a significant role in the pathogenesis of HCV infection, and is clinically recognized as liver inflammation and fibrosis [6,[8][9][10][11][12].…”

Section: Introductionmentioning

confidence: 99%

Distinctive intrahepatic characteristics of paediatric and adult pathogenesis of chronic hepatitis C infection

Valva

Gismondi

Casciato

et al. 2014

Clinical Microbiology and Infection

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Mechanisms leading to liver damage in chronic hepatitis C (CHC) are being discussed, but both the immune system and the virus are involved. The aim of this study was to evaluate intrahepatic viral infection, apoptosis and portal and periportal/interface infiltrate in paediatric and adult patients to elucidate the pathogenesis of chronic hepatitis C. HCV-infected, activated caspase-3(+) and TUNEL(+) hepatocytes, as well as total, CD4(+), CD8(+), Foxp3(+) and CD20(+) lymphocytes infiltrating portal and periportal/interface tracts were evaluated in 27 paediatric and 32 adult liver samples by immunohistochemistry or immunofluorescence. The number of infected hepatocytes was higher in paediatric than in adult samples (p 0.0078). In children, they correlated with apoptotic hepatocytes (activated caspase-3(+) r = 0.74, p < 0.0001; TUNEL(+) r = 0.606, p 0.0017). Also, infected (p = 0.026) and apoptotic hepatocytes (p = 0.03) were associated with the severity of fibrosis. In adults, activated caspase-3(+) cell count was increased in severe hepatitis (p = 0.009). Total, CD4(+), CD8(+) and Foxp3(+) lymphocyte count was higher in adult samples (p < 0.05). Paediatric CD8(+) cells correlated with infected (r = 0.495, p 0.04) and TUNEL(+) hepatocytes (r = 0.474, p = 0.047), while adult ones correlated with activated caspase-3(+) hepatocytes (r = 0.387, p 0.04). In adults, CD8(+) was associated with hepatitis severity (p < 0.0001) and correlated with inflammatory activity (CD8(+) r = 0.639, p 0.0003). HCV, apoptosis and immune response proved to be involved in CHC pathogenesis of both paediatric and adult patients. However, liver injury in paediatric CHC would be largely associated with a viral cytopathic effect mediated by apoptosis, while in adults it would be mainly associated with an exacerbated immune response.

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Altered of apoptotic markers of both extrinsic and intrinsic pathways induced by hepatitis C virus infection in peripheral blood mononuclear cells

Cited by 12 publications

References 44 publications

Increased Spontaneous Programmed Cell Death Is Associated with Impaired Cytokine Secretion in Peripheral Blood Mononuclear Cells from Hepatitis C Virus-Positive Patients

Increased Spontaneous Programmed Cell Death Is Associated with Impaired Cytokine Secretion in Peripheral Blood Mononuclear Cells from Hepatitis C Virus-Positive Patients

Expression of Fas (CD95) and Bcl-2 in peripheral blood mononuclear cells in patients with chronic HCV and schistosomiasis

Distinctive intrahepatic characteristics of paediatric and adult pathogenesis of chronic hepatitis C infection

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