Cited by 53Asthma and respiratory diseasesRespiratory viral infections researchNitric Oxide and Endothelin Effects

Nitric Oxide Inhibits Rhinovirus-Induced Granulocyte Macrophage Colony-Stimulating Factor Production in Bronchial Epithelial Cells

Sanders, Scherer P., Kim, Jean, Ryan Connolly, K., Porter, Jacqueline D., Siekierski, Edward S., Proud, David·2001·American Journal of Respiratory Cell and Molecular Biology

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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Crossref · 10.1165/ajrcmb.24.3.4131

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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.
Venue
American Journal of Respiratory Cell and Molecular Biology
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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