Involvement of Interleukin 6 in Hepatitis B Viral Infection

Xia, Caixia; Liu, Yanning; Chen, Zhi; Zheng, Ming‐Hua

doi:10.1159/000430386

Cited by 51 publications

(37 citation statements)

References 77 publications

(87 reference statements)

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“…An investigation of HBcAg expression in liver tissue revealed predominant cytoplasmic HBcAg associated with higher levels of proliferating cell nuclear antigen (PCNA) [8]. Besides, IL-6 was also reported to be involved in liver regeneration [13, 41]. Taken together, HBcAg might play multiple roles in the progress of HBV-related disease.…”

Section: Discussionmentioning

confidence: 99%

Hepatitis B Virus Core Antigen Stimulates IL-6 Expression via p38, ERK and NF-κB Pathways in Hepatocytes

Chen

et al. 2017

Cell Physiol Biochem

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Background: Hepatitis B virus (HBV) causes both acute and chronic liver injury. Viral proteins are involved in the pathological progress. Hepatitis B core antigen (HBcAg), a component of viral nucleocapsid, is not only essential for HBV lifecycle, but also exhibits strong immunogenicity. The cytoplasmic location of HBcAg in liver biopsy is associated with liver injury and inflammation, but the exact mechanisms remain to be elaborated. Methods: Huh7, SMMC-7721 and L-02 cells were transfected with pEGFP-N1-HBcAg to establish an intracellular HBcAg expression model. The mRNA and protein levels of Interleukin (IL)-6 were detected by qPCR and ELISA respectively. The signaling pathway-related proteins were investigated by western blot and immunofluorescence assay. Results: HBcAg increased the expression and secretion of IL-6 through activating extracellular signal-related kinase (ERK), p38 mitogen-activated protein kinase (p38 MAPK) and nuclear factor-kappa B (NF-κB). These activations can be blocked by specific inhibitors of the three pathways. Conclusions: HBcAg actives p38, ERK1/2 and NF-κB to enhance the production of IL-6 in hepatocytes. This provides a molecular mechanism to explain the association of cytoplasmic HBcAg with severe liver injury and inflammation.

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Section: Discussionmentioning

confidence: 99%

Hepatitis B Virus Core Antigen Stimulates IL-6 Expression via p38, ERK and NF-κB Pathways in Hepatocytes

Chen

et al. 2017

Cell Physiol Biochem

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“…Pro-inflammatory cytokines such as IL-6, IL-8, and TNF-α are involved in HBV- or HCV-induced liver inflammation and treatment outcomes2740414243. The expression levels of these cytokines in HBV/HCV dual infection are unclear.…”

Section: Discussionmentioning

confidence: 99%

“…The immunopathogenesis of viral diseases likely entails cytokine production in response to viral infection by the host27. The co-existence of two chronic viral infections may alter the profile of cytokine production.…”

mentioning

confidence: 99%

HBV/HCV dual infection impacts viral load, antibody response, and cytokine expression differently from HBV or HCV single infection

Chen

Zhang

Wen

et al. 2016

Sci Rep

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Hepatitis B virus/hepatitis C virus (HBV/HCV) dual infection is common among high-risk individuals. To characterize the virological and immunological features of patients with HBV/HCV dual infection, we enrolled 1,049 individuals who have been identified as injection drug users. Patients were divided into single and dual infection groups according to the serological markers. We found the average HCV RNA level was significantly lower; however, HBV viral load was significantly higher in HBV/HCV dual-infected patients (n = 42) comparing HCV single infection (n = 340) or HBV single infection (n = 136). The level of anti-HBs in patients who experienced spontaneous HBV clearance was higher than that in HCV single-infected patients with HBV spontaneous clearance. The level of anti-HCV E2 in HBV/HCV dual infection was lower than that detected in HCV single infection. Serum levels of IL-6, IL-8, and TNF-α were significantly lower in HBV/HCV dual-infected patients than in patients infected with HBV or HCV alone. Taken together, two viral replications are imbalanced in dual infected patients. The anti-HBs and anti-HCV E2 antibody production were impaired and proinflammatory IL-6, IL-8, and TNF-α also downregulated due to dual infection. These findings will help further understanding the pathogenesis of HBV/HCV dual infection.

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“…Many cytokines have been shown to be involved in the HBV infection process [23]. The cytokines IFN-γ, IL-2, TNF-α (Th1-like), and IL-4 and IL-10 (Th2-like) that were secreted in splenocytes obtained from immunized HLA-A2 C57BL/6 mice were analyzed in the presence of HBcAg (10 g/ml).…”

Section: Adv-hbcag-tppii Enhanced Th1-like Cell Secreting Cytokinesmentioning

confidence: 99%

Adenovirus Vector Harboring the HBcAg and Tripeptidyl Peptidase II Genes Induces Potent Cellular Immune Responses In Vivo

Tan¹,

Ma²,

Hu³

et al. 2017

Cell Physiol Biochem

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Background: Chronic hepatitis B virus (HBV) infection is associated with a weak but specific cellular immune response of the host to HBV. Tripeptidyl peptidaseⅡ (TPPⅡ), an intracellular macromolecule and proteolytic enzyme, plays an important complementary and compensatory role for the proteasome during viral protein degradation and major histocompatibility complex class I antigen presentation by inducing a specific cellular immune response in vivo. Based on a previous study, we aimed to explore the role of MHC class I antigen presentation in vivo and the mechanisms that may be involved. Methods: In this study, recombinant adenoviral vectors harboring the hepatitis B core antigen (HBcAg) and the TPPII gene were constructed (Adv-HBcAg and Adv-HBcAg-TPPII), and H-2Kd HBV-transgenic BALB/c mice and HLA-A2 C57BL/6 mice were immunized with these vectors, respectively. We evaluated the specific immune responses induced by Adv-HBcAg-TPPII in the HBV transgenic BALB/c mice and HLA-A2 C57BL/6 mice as well as the anti-viral ability of HBV transgenic mice, and we explored the underlying mechanisms. Results: We found that immunization with Adv-HBcAg-TPPII induced the secretion of the cytokines interleukin-2 (IL-2), interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) as well as the activities of IFN-γ-secreting CD8+ T cells and CD4+ T cells. In addition, HBcAg-specific CTL activity in C57/BL mice and HBV transgenic animals was significantly enhanced in the Adv-HBcAg-TPPII group. Furthermore, Adv-HBcAg-TPPII decreased the hepatitis B surface antigen (HBsAg) and HBV DNA levels and the amount of HBsAg and HBcAg in liver tissues. Moreover, Adv-HBcAg-TPPII enhanced the expression of T-box transcription factor (T-bet) and downregulated GATA-binding protein 3 (GATA-3) while increasing the expression levels of JAK2, STAT1, STAT4 and Tyk2. Conclusions: These results suggested that the JAK/STAT signaling pathway participates in the CTL response that is mediated by the adenoviral vector encoding TPPII. Adv-HBcAg-TPPII could therefore break immune tolerance and stimulate HBV-specific cytotoxic T lymphocyte activity and could have a good therapeutic effect in transgenic mice.

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Involvement of Interleukin 6 in Hepatitis B Viral Infection

Cited by 51 publications

References 77 publications

Hepatitis B Virus Core Antigen Stimulates IL-6 Expression via p38, ERK and NF-κB Pathways in Hepatocytes

Hepatitis B Virus Core Antigen Stimulates IL-6 Expression via p38, ERK and NF-κB Pathways in Hepatocytes

HBV/HCV dual infection impacts viral load, antibody response, and cytokine expression differently from HBV or HCV single infection

Adenovirus Vector Harboring the HBcAg and Tripeptidyl Peptidase II Genes Induces Potent Cellular Immune Responses In Vivo

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