Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
Molecular Medicine Reports
Join Editorial Board Propose a Special Issue
Print ISSN: 1791-2997 Online ISSN: 1791-3004
Journal Cover
July-2023 Volume 28 Issue 1

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
July-2023 Volume 28 Issue 1

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML

  • Supplementary Files
    • Supplementary_Data1.pdf
    • Supplementary_Data2.xlsx
Article Open Access

ATOH8 promotes HBV immune tolerance by inhibiting the pyroptotic pathway in hepatocytes

  • Authors:
    • Xiaofei Liu
    • Zhenyu Fan
    • Liping Chen
    • Jingmao Yang
    • Jilin Cheng
  • View Affiliations / Copyright

    Affiliations: Department of Gastroenterology and Hepatology, Shanghai Public Health Clinical Center, Fudan University, Shanghai 201508, P.R. China, Department of Gastroenterology and Hepatology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, P.R. China
    Copyright: © Liu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 131
    |
    Published online on: May 22, 2023
       https://doi.org/10.3892/mmr.2023.13018
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

The mechanism of hepatitis B virus (HBV) immune tolerance remains unclear. Our previous studies showed that ATOH8 plays an important role in the liver tumor immune microenvironment; however, the specific immune regulatory mechanism requires further studies. Studies have shown that the hepatitis C virus (HCV) can cause hepatocyte pyroptosis; however, the relationship between HBV and pyroptosis is contested. Therefore, this study aimed to determine whether ATOH8 interfered with HBV activity through pyroptosis to further study the mechanism of ATOH8 on immune regulation and enrich our understanding of HBV‑induced invasion. The expression levels of pyroptosis‑related molecules (GSDMD and Caspase‑1) in liver cancer tissues and peripheral blood mononuclear cells (PBMCs) of patients with HBV were assessed using qPCR and western blotting. HepG2.2.15 and Huh7 cells were used to overexpress ATOH8 using a recombinant lentiviral vector. The HBV DNA expression levels in HepG2.2.15 cells were detected using absolute quantitative (q)PCR, and the hepatitis B surface antigen expression levels in the HepG2.2.15 cell culture supernatant were measured using ELISA. The expression of pyroptosis‑related molecules in Huh7 and HepG2.2.15 cells was detected using western blotting and qPCR. Additionally, the expression levels of inflammatory factors including TNF‑α, INF‑α, IL‑18, and IL‑1β were detected using qPCR and ELISA. The liver cancer tissues and PBMCs of patients with HBV showed higher expressions of pyroptosis‑related molecules than those of normal samples. ATOH8‑overexpressed HepG2.2.15 cells had higher HBV expression levels but lower levels of pyroptosis‑related molecules, such as GSDMD and Caspase‑1, than those in the control group. Similarly, the expression levels of pyroptosis‑related molecules in Huh7 cells overexpressing ATOH8 were lower than that in Huh7‑GFP cells. Further detection of the expression of INF‑α and TNF‑α in HepG2.2.15 cells overexpressing ATOH8 showed that ATOH8 overexpression increased the expression of these inflammatory factors, including those associated with pyroptosis (IL‑18 and IL‑1β). In conclusion, ATOH8 promoted HBV immune escape by inhibiting hepatocyte pyroptosis.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

View References

1 

Nicolini LA, Orsi A, Tatarelli P, Viscoli C, Icardi G and Sticchi L: A global view to HBV chronic infection: Evolving strategies for diagnosis, treatment and prevention in immunocompetent individuals. Int J Environ Res Public Health. 16:33072019. View Article : Google Scholar : PubMed/NCBI

2 

Pollicino T and Caminiti G: HBV–Integration studies in the clinic: Role in the natural history of infection. Viruses. 13:3682021. View Article : Google Scholar : PubMed/NCBI

3 

Zhou L, He R, Fang P, Li M, Yu H, Wang Q, Yu Y, Wang F, Zhang Y, Chen A, et al: Hepatitis B virus rigs the cellular metabolome to avoid innate immune recognition. Nat Commun. 12:982021. View Article : Google Scholar : PubMed/NCBI

4 

Wieland S, Thimme R, Purcell RH and Chisari FV: Genomic analysis of the host response to hepatitis B virus infection. Proc Natl Acad Sci USA. 101:6669–6674. 2004. View Article : Google Scholar : PubMed/NCBI

5 

Lebossé F, Testoni B, Fresquet J, Facchetti F, Galmozzi E, Fournier M, Hervieu V, Berthillon P, Berby F, Bordes I, et al: Intrahepatic innate immune response pathways are downregulated in untreated chronic hepatitis B. J Hepatol. 66:897–909. 2017. View Article : Google Scholar : PubMed/NCBI

6 

Luangsay S, Gruffaz M, Isorce N, Testoni B, Michelet M, Faure-Dupuy S, Maadadi S, Ait-Goughoulte M, Parent R, Rivoire M, et al: Early inhibition of hepatocyte innate responses by hepatitis B virus. J Hepatol. 63:1314–1322. 2015. View Article : Google Scholar : PubMed/NCBI

7 

Visvanathan K, Skinner NA, Thompson AJV, Riordan SM, Sozzi V, Edwards R, Rodgers S, Kurtovic J, Chang J, Lewin S, et al: Regulation of toll-like receptor-2 expression in chronic hepatitis B by the precore protein. Hepatology. 45:102–110. 2007. View Article : Google Scholar : PubMed/NCBI

8 

Li M, Sun R, Xu L, Yin W, Chen Y, Zheng X, Lian Z, Wei H and Tian Z: Kupffer cells support hepatitis B virus-mediated CD8+ T cell exhaustion via hepatitis B core antigen-TLR2 interactions in mice. J Immunol. 195:3100–3109. 2015. View Article : Google Scholar : PubMed/NCBI

9 

Teng Y, Xu Z, Zhao K, Zhong Y, Wang J, Zhao L, Zheng Z, Hou W, Zhu C, Chen X, et al: Novel function of SART1 in HNF4α transcriptional regulation contributes to its antiviral role during HBV infection. J Hepatol. 75:1072–1082. 2021. View Article : Google Scholar : PubMed/NCBI

10 

Zhang Y, Chen X, Cao Y and Yang Z: Roles of APOBEC3 in hepatitis B virus (HBV) infection and hepatocarcinogenesis. Bioengineered. 12:2074–2086. 2021. View Article : Google Scholar : PubMed/NCBI

11 

Lak R, Yaghobi R and Garshasbi M: Importance of miR-125a-5p and miR-122-5p expression in patients with HBV infection. Cell Mol Biol (Noisy-le-grand). 66:1–8. 2020. View Article : Google Scholar : PubMed/NCBI

12 

Oropeza CE, Tarnow G, Sridhar A, Taha TY, Shalaby RE and McLachlan A: The regulation of HBV transcription and replication. Adv Exp Med Biol. 1179:39–69. 2020. View Article : Google Scholar : PubMed/NCBI

13 

Xu M, Huang S, Dong X, Chen Y, Li M, Shi W, Wang G, Huang C, Wang Q, Liu Y, et al: A novel isoform of ATOH8 promotes the metastasis of breast cancer by regulating RhoC. J Mol Cell Biol. 13:59–71. 2021. View Article : Google Scholar : PubMed/NCBI

14 

Song Y, Pan G, Chen L, Ma S, Zeng T, Chan THM, Li L, Lian Q, Chow R, Cai X, et al: Loss of ATOH8 increases stem cell features of hepatocellular carcinoma cells. Gastroenterology. 149:1068–1081.e5. 2015. View Article : Google Scholar : PubMed/NCBI

15 

Chen L, Yang J, Wang Y, Wu N, Li X, Li J, Huang Y and Cheng J: ATOH8 overexpression inhibits the tumor progression and monocyte chemotaxis in hepatocellular carcinoma. Int J Clin Exp Pathol. 13:2534–2543. 2020.PubMed/NCBI

16 

Yu P, Zhang X, Liu N, Tang L, Peng C and Chen X: Pyroptosis: Mechanisms and diseases. Signal Transduct Target Ther. 6:1282021. View Article : Google Scholar : PubMed/NCBI

17 

Song L, Pei L, Yao S, Wu Y and Shang Y: NLRP3 inflammasome in neurological diseases, from functions to therapies. Front Cell Neurosci. 11:632017. View Article : Google Scholar : PubMed/NCBI

18 

Pezuk JA: Pyroptosis in combinatorial treatment to improve cancer patients' outcome, is that what we want? EBioMedicine. 41:17–18. 2019. View Article : Google Scholar : PubMed/NCBI

19 

Zhang L, Zeyu W, Liu B, Jang S, Zhang Z and Jiang Y: Pyroptosis in liver disease. Rev Esp Enferm Dig. 113:280–285. 2021.PubMed/NCBI

20 

Ługowska A, Hetmańczyk-Sawicka K, Iwanicka-Nowicka R, Fogtman A, Cieśla J, Purzycka-Olewiecka JK, Sitarska D, Płoski R, Filocamo M, Lualdi S, et al: Gene expression profile in patients with Gaucher disease indicates activation of inflammatory processes. Sci Rep. 9:60602019. View Article : Google Scholar : PubMed/NCBI

21 

Jiang Y, Han Q, Zhao H and Zhang J: The mechanisms of HBV-induced hepatocellular carcinoma. J Hepatocell Carcinoma. 8:435–450. 2021. View Article : Google Scholar : PubMed/NCBI

22 

Yu X, Lan P, Hou X, Han Q, Lu N, Li T, Jiao C, Zhang J, Zhang C and Tian Z: HBV inhibits LPS-induced NLRP3 inflammasome activation and IL-1β production via suppressing the NF-κB pathway and ROS production. J Hepatol. 66:693–702. 2017. View Article : Google Scholar : PubMed/NCBI

23 

Xie WH, Ding J, Xie XX, Yang XH, Wu XF, Chen ZX, Guo QL, Gao WY, Wang XZ and Li D: Hepatitis B virus X protein promotes liver cell pyroptosis under oxidative stress through NLRP3 inflammasome activation. Inflamm Res. 69:683–696. 2020. View Article : Google Scholar : PubMed/NCBI

24 

Wei Q, Mu K, Li T, Zhang Y, Yang Z, Jia X, Zhao W, Huai W, Guo P and Han L: Deregulation of the NLRP3 inflammasome in hepatic parenchymal cells during liver cancer progression. Lab Invest. 94:52–62. 2014. View Article : Google Scholar : PubMed/NCBI

25 

Zarković G: Population growth and planning in Yugoslavia. Nar Zdrav. 28:41–48. 1972.(In Serbian). PubMed/NCBI

26 

Whitsett TL, Levin DC and Manion CV: Comparison of the beta 1 and beta 2 adrenoceptor blocking properties of acebutolol and propranolol. Chest. 82:668–673. 1982. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Liu X, Fan Z, Chen L, Yang J and Cheng J: ATOH8 promotes HBV immune tolerance by inhibiting the pyroptotic pathway in hepatocytes. Mol Med Rep 28: 131, 2023.
APA
Liu, X., Fan, Z., Chen, L., Yang, J., & Cheng, J. (2023). ATOH8 promotes HBV immune tolerance by inhibiting the pyroptotic pathway in hepatocytes. Molecular Medicine Reports, 28, 131. https://doi.org/10.3892/mmr.2023.13018
MLA
Liu, X., Fan, Z., Chen, L., Yang, J., Cheng, J."ATOH8 promotes HBV immune tolerance by inhibiting the pyroptotic pathway in hepatocytes". Molecular Medicine Reports 28.1 (2023): 131.
Chicago
Liu, X., Fan, Z., Chen, L., Yang, J., Cheng, J."ATOH8 promotes HBV immune tolerance by inhibiting the pyroptotic pathway in hepatocytes". Molecular Medicine Reports 28, no. 1 (2023): 131. https://doi.org/10.3892/mmr.2023.13018
Copy and paste a formatted citation
x
Spandidos Publications style
Liu X, Fan Z, Chen L, Yang J and Cheng J: ATOH8 promotes HBV immune tolerance by inhibiting the pyroptotic pathway in hepatocytes. Mol Med Rep 28: 131, 2023.
APA
Liu, X., Fan, Z., Chen, L., Yang, J., & Cheng, J. (2023). ATOH8 promotes HBV immune tolerance by inhibiting the pyroptotic pathway in hepatocytes. Molecular Medicine Reports, 28, 131. https://doi.org/10.3892/mmr.2023.13018
MLA
Liu, X., Fan, Z., Chen, L., Yang, J., Cheng, J."ATOH8 promotes HBV immune tolerance by inhibiting the pyroptotic pathway in hepatocytes". Molecular Medicine Reports 28.1 (2023): 131.
Chicago
Liu, X., Fan, Z., Chen, L., Yang, J., Cheng, J."ATOH8 promotes HBV immune tolerance by inhibiting the pyroptotic pathway in hepatocytes". Molecular Medicine Reports 28, no. 1 (2023): 131. https://doi.org/10.3892/mmr.2023.13018
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team