Nitric oxide inhibits rhinovirus-induced granulocyte macrophage colony-stimulating factor production in bronchial epithelial cells.
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-kappa 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.
Division of Pulmonary and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. ssanders@welch.jhu.edu
S P
SP
Sanders
J
J
Kim
K R
KR
Connolly
J D
JD
Porter
E S
ES
Siekierski
D
D
Proud
D000818:Animals; D001980:Bronchi / Q000502:physiology* / Q000821:virology; D002460:Cell Line; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis / Q000235:genetics*; D006801:Humans; D007700:Kinetics; D009569:Nitric Oxide / Q000502:physiology*; D020030:Nitric Oxide Donors / Q000494:pharmacology*; D009687:Nuclear Proteins / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D020545:Respiratory Mucosa / Q000187:drug effects / Q000502:physiology* / Q000821:virology*; D012229:Rhinovirus / Q000187:drug effects / Q000502:physiology*; D013997:Time Factors; D014779:Virus Replication / Q000187:drug effects
D016207:Cytokines; D020030:Nitric Oxide Donors; D009687:Nuclear Proteins; D012333:RNA, Messenger; D009569:Nitric Oxide; D016178:Granulocyte-Macrophage Colony-Stimulating Factor