Nitric Oxide Inhibits Rhinovirus-Induced Granulocyte Macrophage Colony-Stimulating Factor Production in Bronchial Epithelial Cells
Abstract
Infection of asthmatics with human rhinovirus (HRV) enhances airway eosinophilia and airways hyperreactivity. The current studies were performed to further characterize HRV-induced generation by human bronchial epithelial cells of granulocyte macrophage colony-stimulating factor (GM-CSF), a cytokine that could contribute to airway eosinophilia by increasing the survival and activation of eosinophils, and to determine the effects of the antiviral agent nitric oxide (NO) on HRV-induced GM-CSF production. Maximal levels of messenger RNA (mRNA) for GM-CSF were seen 1 h after HRV infection. Expression was sustained through 24 h and declined by 48 h. GM-CSF protein was detected in cell supernatants by 2 h after infection and reached maximal concentrations by 24 h, with the most rapid rate of production occurring from 2 to 7 h. The NO donor 3-(2-hydroxy-2-nitroso-1-propyl-hydrazino)-1-propanamine (NONOate) inhibited HRV-induced GM-CSF protein production in a time- and dose-dependent fashion. NONOate also inhibited HRV-induced GM-CSF mRNA levels at both times (1 and 4 h) examined. NONOate increased GM-CSF mRNA stability, suggesting that reduced mRNA levels were due to inhibition of transcription. The transcription factor nuclear factor-κ B was rapidly induced by HRV infection, but was not inhibited by NONOate, implying a role for other transcription factors. Thus, NO may play an important anti-inflammatory role in virally induced exacerbations of diseases such as asthma.
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Fibrinogen enhances adherence of group A streptococcus to influenza A virus-infected cells.
“Fibrinogen, for instance, enhances adherence of group A streptococcus to influenza A virus-infected cells (249).”
From The airway epithelium: soldier in the fight against respiratory viruses (2011) · cites this paper as [249]
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- Authors
- Sanders, S. P., Kim, J., Ryan Connolly, K., Porter, J. D., Siekierski, E. S., & Proud, D.
- Affiliations
- Johns Hopkins University (US)
- Division of Pulmonary and Critical Care Medicine; Division of Allergy and Clinical Immunology, Department of Medicine; and Department of Otolaryngology—Head & Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland
- Corresponding author
- Sanders, Scherer P.
- ORCID
- Proud, David
- Venue
- American Journal of Respiratory Cell and Molecular Biology
- Publisher
- Oxford University Press (OUP)
- Published
- 2001-03-01
- Volume
- 24
- Issue
- 3
- Pages
- 317-325
- ISSN
- 1044-1549 (ISSN-L)
- 1535-4989
- OpenAlex
- W1981265301
- Cited by
- 53
- References
- 36
- Citations by year
- 2025: 3 · 2023: 1 · 2022: 3 · 2019: 2 · 2018: 2 · 2016: 2 · 2015: 1 · 2013: 1 · 2012: 1
- FWCI
- 2.16
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Journal of Respiratory Cell and Molecular Biology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5p01ai037163-07, 5r01hl061011-02)
- National Heart, Lung, and Blood Institute (HL 61011)
- National Institute of Allergy and Infectious Diseases (AI 37163)
- Topics
- Health Sciences › Medicine › Physiology › Asthma and respiratory diseases
- Health Sciences › Medicine › Epidemiology › Respiratory viral infections research
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Keywords
- nitric oxide, human rhinovirus, GM-CSF, bronchial epithelial cells, NONOates, airway eosinophilia, asthma, viral infection, mRNA stability, transcriptional regulation, nuclear factor-kappaB, eosinophils, airway inflammation
- MeSH terms
- Animals, Bronchi, Cell Line, Cells, Cultured, Gene Expression Regulation, Humans, Kinetics, Nitric Oxide, Nuclear Proteins, Rhinovirus, RNA, Messenger, Time Factors, Virus Replication, Granulocyte-Macrophage Colony-Stimulating Factor, Cytokines, Nitric Oxide Donors, Respiratory Mucosa
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