Cited by 515Influenza Virus Research StudiesRespiratory viral infections researchinterferon and immune responses

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Proinflammatory cytokine responses induced by influenza A (H5N1) viruses in primary human alveolar and bronchial epithelial cells

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Chan, MCW, Cheung, CY, Chui, WH, Tsao, SW, Nicholls, JM, Chan, YO, Chan, RWY, Long, HT, Poon, LLM, Guan, Y, Peiris, JSM·2005·Respiratory Research

DOI 10.1186/1465-9921-6-135PMC PMC1318487

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Abstract

Background: Fatal human respiratory disease associated with influenza A subtype H5N1 has been documented in Hong Kong, and more recently in Vietnam, Thailand and Cambodia. We previously demonstrated that patients with H5N1 disease had unusually high serum levels of IP-10 (interferon-gamma-inducible protein-10). Furthermore, when compared with human influenza virus subtype H1N1, the H5N1 viruses in 1997 (A/Hong Kong/483/97) (H5N1/97) were more potent inducers of pro-inflammatory cytokines (e.g. tumor necrosis factor-a) and chemokines (e.g. IP-10) from primary human macrophages in vitro, which suggests that cytokines dysregulation may play a role in pathogenesis of H5N1 disease. Since respiratory epithelial cells are the primary target cell for replication of influenza viruses, it is pertinent to investigate the cytokine induction profile of H5N1 viruses in these cells. Methods: We used quantitative RT-PCR and ELISA to compare the profile of cytokine and chemokine gene expression induced by H5N1 viruses A/HK/483/97 (H5N1/97), A/Vietnam/1194/04 and A/Vietnam/3046/04 (both H5N1/04) with that of human H1N1 virus in human primary alveolar and bronchial epithelial cells in vitro. Results: We demonstrated that in comparison to human H1N1 viruses, H5N1/97 and H5N1/04 viruses were more potent inducers of IP-10, interferon beta, RANTES (regulated on activation, normal T cell expressed and secreted) and interleukin 6 (IL-6) in primary human alveolar and bronchial epithelial cells in vitro. Recent H5N1 viruses from Vietnam (H5N1/04) appeared to be even more potent at inducing IP-10 than H5N1/97 virus. Conclusion: The H5N1/97 and H5N1/04 subtype influenza A viruses are more potent inducers of proinflammatory cytokines and chemokines in primary human respiratory epithelial cells than subtype H1N1 virus. We suggest that this hyper-induction of cytokines may be relevant to the pathogenesis of human H5N1 disease.

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Authors: Chan, M., Cheung, C., Chui, W., Tsao, S., Nicholls, J., Chan, Y., Chan, R., Long, H., Poon, L., Guan, Y., & Peiris, J.
Affiliations: Queen Mary Hospital (CN)
Grantham Hospital (CN)
University of Hong Kong (HK)
National Institute Of Hygiene And Epidemiology (VN)
Corresponding author: Peiris, JSM
ORCID: Guan, Y
Venue: Respiratory Research
Publisher: Springer Science and Business Media LLC
Published: 2005-11-11
Volume: 6
Issue: 1
Pages: 135-135
ISSN: 1465-9921 (ISSN-L)
1465-993X
DOI: 10.1186/1465-9921-6-135
PMC: PMC1318487
OpenAlex: W2122988122
Cited by: 510
References: 37
Citations by year: 2026: 7 · 2025: 16 · 2024: 16 · 2023: 10 · 2022: 10 · 2021: 23 · 2020: 24 · 2019: 14 · 2018: 20 · 2017: 19 · 2016: 16 · 2015: 21 · 2014: 26 · 2013: 36 · 2012: 26
FWCI: 20.18
Type: journal article
Language: en
Open access: gold
doi.org
Licence: cc-by
www.springer.com/tdm (unspecified)
Locations: Respiratory Research (publishedVersion, cc-by)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
The HKU Scholars Hub (University of Hong Kong) (submittedVersion, cc-by-nc-nd)
Greater South Information System
Funders: University of Hong Kong
Topics: Health Sciences › Medicine › Epidemiology › Influenza Virus Research Studies
Health Sciences › Medicine › Epidemiology › Respiratory viral infections research
Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
Keywords: H5N1 avian influenza, influenza A virus, inflammatory cytokines, chemokines, CXCL10, interferon-beta, RANTES, interleukin-6, alveolar epithelial cells, bronchial epithelial cells, respiratory epithelium, cytokine imbalance, viral pathogenesis
MeSH terms: Bronchi, Cells, Cultured, Epithelial Cells, Humans, Immunologic Factors, Pulmonary Alveoli, Cytokines, Respiratory Mucosa, Influenza A Virus, H1N1 Subtype, Influenza A Virus, H5N1 Subtype

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Proinflammatory cytokine responses induced by influenza A (H5N1) viruses in primary human alveolar and bronchial epithelial cells

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