Up-regulation of IL-12 expression in patients with chronic hepatitis B is mediated by the PI3K/Akt pathway

Wang, Hongwei; Gao, Haili; Wei, Xiaoxia; Wang, Xinhong

doi:10.1007/s11010-015-2463-6

Cited by 15 publications

(14 citation statements)

References 33 publications

(31 reference statements)

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“…During HBV infection, the PI3K/Akt pathway was activated [57]. IL-12, as one of the proin ammatory factors, signi cantly increase in CHB patients and HBVinduced IL-12 expression involved into the activation of the PI3K-Akt pathway [29]. In addition, the evidence has demonstrated that the change of PTEN activity leads to development of CHB by deregulating the PI3K/Akt pathway [58].…”

Section: Discussionmentioning

confidence: 99%

“…Recruiting 3-phosphoinositide dependent kinase-1(PDK1) to cell membrane is regulated by PI3K promoting the activation of protein kinase B(Akt), and forms PI3K/PDK1/Akt signaling pathway [27,28]. The activation of PI3K/Akt pathway also increases IL-12 production, which is a typical proin ammatory cytokine of CHB [29]. Research indicated that the lack or decrease of PTEN caused increase of PI3K [30], thus, elevated the level of PDK1 and Akt in the downstream [31,32].…”

Section: Introductionmentioning

confidence: 99%

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Research on the Pathogenesis of Chronic Hepatitis B: From T lymphocyte to HMGB1-PTEN Pathway

Liu

et al. 2020

Preprint

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Background: Viral hepatitis is still a major health problem in the world, such as chronic hepatitis B(CHB). Hepatitis B virus (HBV) easily causes liver cirrhosis and hepatocellular carcinoma that seriously endanger human health. However, the cellar and molecular pathology of hepatitis B virus is still unclear. Currently, the level of immunity and the inflammatory response are recognized as close relationship with the prognosis of CHB. Methods: Peripheral blood samples from 36 CHB patients and 14 healthy volunteers as control subjects in this study. We studied the change of T lymphocytes and the proteins levels of HMGB1-PTEN pathway in the CHB patients and the healthy controls by Flow cytometry and enzyme-linked immunosorbent assay (Elisa), and then further analyzed the correlation between T lymphocytes and HMGB1-PTEN pathway by constructing multiple regression equation and Pearson test. Results: The percentages of CD4+T, CD8+T cells in CHB patients were lower than those of the healthy controls, and the percentages of Th17, Treg, ratio of Th17/Treg and Tfh cells in CHB patients were higher than those of the healthy controls (P<0.01). HMGB1, PI3K, PDK1, Akt proteins in CHB patients were higher than healthy people (P<0.01). Furthermore, HMGB1-PTEN pathway proteins were negatively correlated with CD4+T, CD8+T cells, and positively correlated with Th17, Treg cells. Conclusions: Long term HBV infection could lead to decrease of immune function and activation of inflammatory response, which makes it difficult to cure chronic hepatitis B.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Research on the Pathogenesis of Chronic Hepatitis B: From T lymphocyte to HMGB1-PTEN Pathway

Liu

et al. 2020

Preprint

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“…The medium was supplemented with 10% FBS, 100 IU/mL penicillin, and 100 IU/mL streptomycin. Cells were changed into fresh medium every third day, and split by trypsinization at a confluence of about 90%[15]. AD38 cells, which are a variant of HepG2 cells, express the HBV genome under the control of a tetracycline (Tet)-off promoter.…”

Section: Methodsmentioning

confidence: 99%

Hepatitis B virus upregulates host expression of α-1,2-mannosidasesviathe PPARα pathway

Hu¹,

Jiang²,

Zou³

et al. 2016

WJG

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AIMTo assess the effects of hepatitis B virus (HBV) on the expression of host α-1,2-mannosidases and determine the underlying mechanisms.METHODSWe measured the expression levels of MAN1A1, MAN1A2, MAN1B1, and MAN1C1 in cell lines HepG2.2.15, HepN10, HepAD38 and HepG2 by Western blot. Viral antigens (HBsAg and HBeAg) in the culture medium were measured using the chemiluminescence method. HBV DNA quantification assays were performed using a commercial real-time PCR kit. Protein levels of human liver tissue α-1,2-mannosidases were also evaluated by Western blot. Plasmids containing seven individual viral genes of HBV (PTT22-HBx, PTT22-HBs, PTT22-preS2, PTT22-preS1, PTT22-HBc, PTT22-HBe, and PTT22-HBp) or control plasmids (PTT22-vector) were transfected into HepG2 cells. MK886 (PPARα) and GW9662 (PPARγ) inhibitors were used to explore the effects of HBV on α-1,2-mannosidase expression after the PPARα and PPARγ pathways were blocked.RESULTSWe showed that the expression of α-1,2-mannosidases was higher in stably transfected HBV cells than in controls. The expression levels of α-1,2-mannosidase were higher in AD38 cells than those in ND10 cells, which were in turn greater than those in G2.2.15 cells, and positively correlated with the expression of HBsAg in all the cell lines. Levels of α-1,2-mannosidase in non-tumorous liver tissues of HBV-related HCC patients were also higher than in the tissues from non-HBV-related HCC patients. Moreover, transfecting HepG2 cells with a component of the HBV viral envelope also increased the expression of α-1,2-mannosidases. However, this envelope protein component could not induce MAN1C1 expression in the presence of a PPARα inhibitor, MK886. We also found that MK886 did not affect the expression of MAN1C1 in AD38 cells without tetracycline in the culture medium. This phenomenon was not observed in the case of GW9662.CONCLUSIONOur results indicate that HBV increases the expression of α-mannosidases both in vitro and in vivo via activation of the PPARα pathway by its envelope protein.

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“…Pro-inflammatory interleukin-12 (IL-12) signalling is the most significant inflammatory pathway associated with HBx (Table S3). IL-12 is upregulated by HBx via the activation of the PI3K/AKT signalling pathway, which could lead to a chronic inflammatory environment (Wang et al, 2015) .…”

Section: Hbv Genes Associated With Hccmentioning

confidence: 99%

Comprehensive review of Hepatitis B Virus‐associated hepatocellular carcinoma research through text mining and big data analytics

et al. 2018

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PubMed was text mined to glean insights into the role of Hepatitis B virus (HBV) in hepatocellular carcinoma (HCC) from the massive number of publications (9249) available to date. Reports from ∼70 countries identified >1300 human genes associated with either the Core, Surface or X gene in HBV-associated HCC. One hundred and forty-three of these host genes, which can potentially yield 1180 biomolecular interactions, each were reported in at least three different publications to be associated with the same HBV. These 143 genes function in 137 pathways, involved mainly in the cell cycle, apoptosis, inflammation and signalling. Fourteen of these molecules, primarily transcriptional regulators or kinases, play roles in several pathways pertinent to the hallmarks of cancers. 'Chronic' was the most frequent word used across the 9249 abstracts. A key event in chronic HBV infection is the integration of HBV into the host genome. The advent of cost-effective, next-generation sequencing technology facilitated the employment of big-data analytics comprehensively to characterize HBV-host integration within HCC patients. A total of 5331 integration events were reported across seven publications, with most of these integrations observed between the Core/X gene and the introns of genes. Nearly one-quarter of the intergenic integrations are within repeats, especially long interspersed nuclear elements (LINE) repeats. Integrations within 13 genes were each reported by at least three different studies. The human gene with the most HBV integrations observed is the TERT gene where a total of 224 integrations, primarily at its promoter and within the tumour tissue, were reported by six of seven publications. This unique review, which employs state-of-the-art text-mining and data-analytics tools, represents the most complete, systematic and comprehensive review of nearly all the publications associated with HBV-associated HCC research. It provides important resources to either focus future research or develop therapeutic strategies to target key molecules reported to play important roles in key pathways of HCC, through the systematic analyses of the commonly reported molecules associated with the various HBV genes in HCC, including information about the interactions amongst these commonly reported molecules, the pathways in which they reside as well as detailed information regarding the viral and host genes associated with HBV integration in HCC patients. Hence this review, which highlights pathways and key human genes associated with HBV in HCC, may facilitate the deeper elucidation of the role of HBV in hepato-carcinogenesis, potentially leading to timely intervention against this deadly disease.

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Up-regulation of IL-12 expression in patients with chronic hepatitis B is mediated by the PI3K/Akt pathway

Cited by 15 publications

References 33 publications

Research on the Pathogenesis of Chronic Hepatitis B: From T lymphocyte to HMGB1-PTEN Pathway

Research on the Pathogenesis of Chronic Hepatitis B: From T lymphocyte to HMGB1-PTEN Pathway

Hepatitis B virus upregulates host expression of α-1,2-mannosidasesviathe PPARα pathway

Comprehensive review of Hepatitis B Virus‐associated hepatocellular carcinoma research through text mining and big data analytics

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