Up-regulation of anti-apoptotic Bcl-2 was slightly lower in cells treated with HCV core, but signal transducer and activator of transcription 5 (STAT5) activation was increased, suggesting dysregulation downstream of STAT activation.
In this setting, it may be hypothesized that inflammatory cytokines stimulate proliferation and transformation of IgH-BCL2 clones that are increased during chronic HCV infection.
Furthermore, IL-7 induced B cell lymphoma 2 (BCL-2) expression and cell cycling of CD56<sup>bright</sup> NK cells, and this effect was impaired in HCV- and HIV-infected subjects.
Further, follow-up from <i>in vitro</i> analysis suggested that the antiapoptosis Bcl2 protein, proliferation-related cyclin D1 protein, and CSC-associated Hes1, Notch1, Nanog, and Sox2 proteins are enhanced during infection or ectopic expression of HCV core protein.<b>IMPORTANCE</b> Endoglin plays a crucial role in fibrogenesis and angiogenesis and is an important protein for tumor growth, survival, and cancer cell metastasis.
In addition, camel milk elevated significantly (P < 0.001) the serum levels of albumin, the antiapoptotic protein BCL-2, the total antioxidant capacity, interleukin-10, and vitamin D. In conclusion, our study revealed a regulatory function of camel milk on multiple parameters of inflammatory mediators, immunomodulators, antiapoptosis, and antioxidants, giving insight into the potential therapeutic benefit underlying the anti-HCV actions of camel milk.
Thus, we reveal a novel mechanism underlying HCV pathogenesis in which multiple intracellular signaling cascades are cooperatively involved in the activation of two important cellular factors, MMP-2 and Bcl-2, in response to HCV infection.
We conclude that BCL-2 gene polymorphism at codon 43 (127G/A) is a new biological marker to potentially identify responders and non-responders of HCV genotype 4 patients to achieving a sustained virological response to treatment with IFN in combination with ribavirin.
Following ex vivo viral adsorption, both HFH/Bcl-2-HUVEC and Huh-7.5/Bcl-2-HUVEC co-implants sustained HCV Jc1 infection for at least 2 weeks in vivo, based on qRT-PCR and immunoelectron microscopic (IEM) analyses of gel tissue.
Our data support the notion that among gastrointestinal MALT lymphomas, t(14;18)-(IgH;Bcl-2) translocation clusters in HCV-positive patients sustaining the role of HCV infection in the lymphoma development.
In contrast, HCV-specific CD8(+) T cells in acute infections evolving to chronicity expressed low levels of CD127 and Bcl-2, exhibited diminished proliferation and cytokine production, and eventually disappeared from the periphery.
Archival liver biopsy specimens of chronic HCV-infection (n = 46) and normal histology (n = 5) were analyzed by immunohistochemistry using antibodies against proliferation marker Mcm-2, G1 phase marker Cyclin D1, S phase marker Cyclin A, cell cycle regulators p21 (CDK inhibitor) and p53 (tumor suppressor protein), apoptotic protein Caspase-3 and anti-apoptotic protein Bcl-2.
Polymerase chain reaction (PCR) amplification assays for Bcl-2/IgH rearrangement were performed on nucleic acids extracted from portal tract inflammatory infiltrates, isolated with laser capture microdissection (LCM), from liver biopsy sections of 16 hepatitis C virus (HCV)-infected patients with and without extrahepatic B cell-related disorders.
Incubation of all cell lines with Bcl-2 siRNA reduced cell viability 96 h after 5-FU treatment compared with all other controls: Huh-7 (P < 0.01), Huh-7 with hepatitis C replicon (P < 0.01), HepG2 (P < 0.01), HLE (P < 0.05).
Results of the present study indicate that the classical form of t(14;18)(q32;q21) involving fusion of IGH with bcl-2 can be detectable in a subset of MALT lymphomas in patients with hepatitis C virus (HCV) infection.
Rearrangement of bcl-2 was observed in 28 of 37 (75.7%) patients with mixed cryoglobulinemia (65% of those with type III disease and 85% of those with type II disease, including 3 of 4 patients with lymphoma) and in 38 of 101 (37.6%) patients with chronic HCV infection but not mixed cryoglobulinemia (P < 0.001).
Therefore, we investigated a possible mechanism of lymphomagenesis, the occurrence of bcl-2 and immunoglobulin gene rearrangement (IgH) in HCV-infected patients.
The precise role of apoptosis in the pathogenesis of hepatitis C-related liver injury remains unclear, but its induction may be related to downregulation of bcl-2 expression associated with ethanol consumption.
These data indicate that t(14;18) and bcl-2 over-expression in lymphoid cells are frequent in chronic HCV infection and suggest that this event may contribute to the pathogenesis of HCV-related lymphoproliferative disorders.
We hypothesized that a mechanism that could account for increased hepatocellular carcinoma in patients with hepatitis C and cirrhosis is selection of bcl-2 expressing cells.