Expression of pro‐ and anti‐inflammatory cytokines in relation to apoptotic genes in Egyptian liver disease patients associated with HCV‐genotype‐4

Zekri, Abdel‐Rahman N.; Bahnassy, Abeer A.; Abdel-Wahab, Sabrin; Khafagy, Medhat; Loutfy, Samah A.; Radwan, Hessam; Shaarawy, Sabry

doi:10.1111/j.1440-1746.2008.05699.x

Cited by 25 publications

(24 citation statements)

References 38 publications

(74 reference statements)

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“…The intrahepatic mRNA levels of IFN-inducible T cell alpha chemoattractant (I-TAC), another CXCR3 chemokine ligand, correlate with both portal and lobular inflammation. Several investigators found that the intrahepatic CXCL10/IP-10 mRNA expression was associated with increased lobular necroinflammation (Harvey et al, 2003;Zekri et al, 2009). Our results showed overexpression of CXCR3 gene in 75% of HCC cases.…”

Section: Discussionsupporting

confidence: 68%

Molecular Prognostic Profile of Egyptian HCC Cases Infected with Hepatitis C Virus

Zekri

Hassan²,

Bahnassy³

et al. 2012

Asian Pacific Journal of Cancer Prevention

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Background: Hepatocellular carcinoma (HCC) is a common and aggressive malignancy. Despite of the improvements in its treatment, HCC prognosis remains poor due to its recurrence after resection. This study provides complete genetic profile for Egyptian HCC. Genome-wide analyses were performed to identify the predictive signatures. Patients and Methods: Liver tissue was collected from 31 patients with diagnosis of HCC and gene expression levels in the tumours and their adjacent non-neoplastic tissues samples were studied by analyzing changes by microarray then correlate these with the clinico-pathological parameters. Genes were validated in an independent set by qPCR. The genomic profile was associated with genetic disorders and cancer focused on gene expression, cell cycle and cell death. Molecular profile analysis revealed cell cycle progression and arrest at G2/M, but progression to mitosis; unregulated DNA damage check-points, and apoptosis. Result: Nine hundred fifty eight transcripts out of the 25,000 studied cDNAs were differentially expressed; 503 were up-regulated and 455 were down-regulated. A total of 19 pathways were up-regulated through 27 genes and 13 pathways were down-regulated through 19 genes. Thirty-seven genes showed significant differences in their expression between HCC cases with high and low Alpha Feto Protein (AFP ≥600 IU/ml). The validation for the microarray was done by real time PCR assay in which PPP3CA, ATG-5, BACE genes showed down-regulation and ABCG2, RXRA, ELOVL2, CXR3 genes showed up-regulation. cDNA microarrays showed that among the major upregulated genes in HCC are sets. Conclusion: The identified genes could provide a panel of new diagnostic and prognostic aids for HCC.

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Section: Discussionsupporting

confidence: 68%

Molecular Prognostic Profile of Egyptian HCC Cases Infected with Hepatitis C Virus

Zekri

Hassan²,

Bahnassy³

et al. 2012

Asian Pacific Journal of Cancer Prevention

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“…However, reduced expression of GSK3b (GSK3B), TNFa, TNF-R I, TNF-R II, and IL10 can be observed in HCC and in other liver diseases (Zekri et al 2009). It is also well accepted that estrogen functions as an immunomodulator with a bidirectional effect on cytokine production: at high concentrations, E 2 decreases the production of pro-inflammatory cytokines including TNFa and IL1b (ILB1) (Ito et al 2001, Hsieh et al 2007), whereas at low concentrations, it increases the production of TNFa and IL1b (Roby & Hunt 1994).…”

Section: Introductionmentioning

confidence: 99%

Estrogen receptor α (ESR1) over-expression mediated apoptosis in Hep3B cells by binding with SP1 proteins

Tu¹,

Velmurugan

Day

et al. 2013

Journal of Molecular Endocrinology

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Previous studies have reported that estrogen receptors (ERs) are expressed in normal human liver, chronic hepatitis, and benign hepatic tumor tissues. However, decreased expression of ERs can be observed in hepatocellular carcinoma (HCC) and the role of ERs in HCC is not fully understood. Thus, the present study aimed to investigate the molecular mechanism induced by the overexpression of ERa (ERa (ESR1)) in Hep3B cells. We first detected the induction of apoptosis in ER-negative Hep3B cells using DNA fragmentation assay and flow cytometry. We found that ERa and ERa plus 17b-estradiol treatment increased apoptosis in Hep3B cells. Additionally, western blotting showed increased expression of active caspase 3 and tumor necrosis factor a (TNFa (TNF)) in ERa-transfected cells. To further understand the importance of SP1-binding sites in the TNFa promoter, ERa-negative Hep3B cells were co-transfected with ERa and a wild-type TNFa plasmid or TNFa with deleted SP1 regions. Deletion of both distant and primal SP1 sites abolished the activity of ERa, and similar results were observed by blocking the expression of SP1 protein using mithramycin (MA). This result indicates that SP1 protein is essential for ERa-activated TNFa promoter activity. Co-immunoprecipitation assay further confirmed the binding interaction between ERa and SP1 in a ligand-dependent manner.In general, we demonstrate that the overexpression of ERa mediates apoptosis in ERa-negative Hep3B cells by the binding of ERa to SP1 protein. Additionally, this ERa-SP1 complex binds to the proximal and distal sites of the TNFa gene promoter and further induces the expression of active caspase 3 in a ligand-dependent manner.

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“…There are more cases of HCV and endemic chronic HCV infection in Egypt than in any other country worldwide [6]. The highest prevalence rate worldwide has been reported in Egypt (15%), where HCV genotype-4 represented 90% of all HCV cases [5,7].…”

Section: Introductionmentioning

confidence: 99%

Endogenous IFNγ in chronic HCV genotype 4 patients treated with PEG-IFNα and ribavirin

Sadeq

Mohtady

Badawy

et al. 2013

J Infect Dev Ctries

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Introduction: Hepatitis C virus (HCV) infections remain an increasingly prevalent and emergent health problem worldwide, causing a wide spectrum of liver diseases. Combination therapy with pegylated interferon (PEG-IFN) of peginterferon alfa-2a and oral ribavirinis currently recognized as the standard treatment of chronic HCV infection. Several complex immunological mechanisms are involved during the course of HCV treatment using interferons. The role of endogenous interferon gamma (IFNγ) in Egyptian patients infected with chronic HCV and treated with PEG-IFN/ribavirin is uncertain. The goal of this study was to evaluate the association of IFNγ and chronic HCV infection among patients treated with combination therapy of PEG-IFN/ribavirin. Methodology: Samples from 20 patients infected with HCV genotype-4 (HCV-4) and 20 non-infected individuals as healthy controls were used in this retrospective study. IFNγ levels in peripheral blood monocytes were analyzed, along with liver enzyme alanine aminotransferase (ALT) levels, and single nucleotide polymorphism (SNP) of the myxovirus resistance-A (MxA) gene. Results: The results showed that an increase of IFNγ and a decrease of ALT levels in chronic HCV-infected patients after 12 weeks of treatment with combination therapy. Conclusion: Enhanced IFNγ secretion and decreased liver enzyme ALT production are indicative of HCV clearance and improvement of liver function. In addition, the SNP of the MxA gene is an important host genetic factor that independently influenced the response to IFNα in patients with chronic HCV infection, especially in those with a low viral load.

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Expression of pro‐ and anti‐inflammatory cytokines in relation to apoptotic genes in Egyptian liver disease patients associated with HCV‐genotype‐4

Cited by 25 publications

References 38 publications

Molecular Prognostic Profile of Egyptian HCC Cases Infected with Hepatitis C Virus

Molecular Prognostic Profile of Egyptian HCC Cases Infected with Hepatitis C Virus

Estrogen receptor α (ESR1) over-expression mediated apoptosis in Hep3B cells by binding with SP1 proteins

Endogenous IFNγ in chronic HCV genotype 4 patients treated with PEG-IFNα and ribavirin

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