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Human Rhinovirus Infection Induces Airway Epithelial Cell Production of Human β-Defensin 2 Both In Vitro and In Vivo
Abstract
We hypothesized that airway epithelial cells, the primary site of human rhinovirus (HRV) infection, provide a link between the innate and specific immune response to HRV via production of human β-defensin (HBD)-2, a potent in vitro attractant and activator of immature dendritic cells. Infection of primary cultures of human epithelial cells with several HRV serotypes induced expression of HBD-2 mRNA and protein, indicating that HBD-2 production was independent of viral receptor usage or mechanisms of viral RNA internalization. Induction of HBD-2 was dependent upon viral replication and could be mimicked by transfection of cells with synthetic dsRNA, but was not dependent upon epithelial production of IL-1. Studies with stable epithelial cell lines expressing HBD-2 promoter constructs, as well as inhibitor studies in primary cells, both demonstrated that induction of HBD-2 involves activation of the transcription factor, NF-κB. Other transcription factors must also be activated by HRV infection, however, as expression of HBD-3 mRNA was also induced and there is no putative NF-κB recognition sequence in the promoter of this gene. HBD-2 showed no direct antiviral activity against HRV. In vivo infection of normal human subjects with HRV-16 induced expression of mRNA for HBD-2 in nasal epithelial scrapings. Increases in mRNA correlated with viral titer and with increased levels of HBD-2 protein in nasal lavages. This represents the first demonstration that HRV infection induces epithelial expression of HBD-2 both in vitro and in vivo, and supports the concept that HBD-2 may play a role in host defense to HRV infection.
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“Abnormal repair processes of the airway epithelium leading to abnormal organization and integrity of the respiratory epithelium, with subsequent perturbations in innate immune functions, have been proposed as key mechanisms in the pathogenesis of chronic airway diseases such as asthma (38, 48) and COPD (221).”
From The airway epithelium: soldier in the fight against respiratory viruses (2011) · cites this paper as [221]
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Metadata
- Authors
- Proud, D., Sanders, S. P., & Wiehler, S.
- Affiliations
- University of Calgary (CA)
- Johns Hopkins University (US)
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2004-04-01
- Volume
- 172
- Issue
- 7
- Pages
- 4637-4645
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- OpenAlex
- W2115289014
- Cited by
- 154
- References
- 64
- Citations by year
- 2025: 5 · 2024: 2 · 2023: 1 · 2022: 1 · 2021: 5 · 2020: 6 · 2019: 4 · 2018: 10 · 2017: 5 · 2016: 9 · 2015: 10 · 2014: 4 · 2013: 6 · 2012: 7
- FWCI
- 8.54
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Immunology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r01hl061011-02)
- National Heart, Lung, and Blood Institute (HL 61011)
- Topics
- Life Sciences › Immunology and Microbiology › Microbiology › Antimicrobial Peptides and Activities
- Health Sciences › Medicine › Epidemiology › Respiratory viral infections research
- Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
- Keywords
- human rhinovirus, human beta-defensin 2, airway epithelial cells, innate immunity, NF-κB, human beta-defensin 3, viral replication, double-stranded RNA, nasal epithelium, host defense, dendritic cell activation
- MeSH terms
- Adult, Common Cold, Female, Humans, Interleukin-1, Male, Promoter Regions, Genetic, Rhinovirus, RNA, Messenger, RNA, Viral, Serotyping, Time Factors, Virus Replication, NF-kappa B, Respiratory Mucosa, beta-Defensins, Virus Inactivation, Cell Line, Tumor
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