Inducible NO synthase expression is low in airway epithelium from young children with cystic fibrosis
Background: This is the first study to measure inducible nitric oxide synthase (iNOS) gene and protein expression quantitatively in primary epithelial cells from very young children with cystic fibrosis (CF). Low levels of exhaled nitric oxide (NO) in CF suggest dysregulation of NO production in the...
| Main Authors: | , , , , , , , , , |
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| Format: | Journal Article |
| Language: | English |
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B M J PUBLISHING GROUP
2006
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| Subjects: | |
| Online Access: | http://hdl.handle.net/20.500.11937/76828 |
| _version_ | 1848763770829012992 |
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| author | Moeller, A. Horak, F. Lane, C. Knight, D. Kicic, Anthony Brennan, S. Franklin, P. Terpolilli, J. Wildhaber, J.H. Stick, S.M. |
| author_facet | Moeller, A. Horak, F. Lane, C. Knight, D. Kicic, Anthony Brennan, S. Franklin, P. Terpolilli, J. Wildhaber, J.H. Stick, S.M. |
| author_sort | Moeller, A. |
| building | Curtin Institutional Repository |
| collection | Online Access |
| description | Background: This is the first study to measure inducible nitric oxide synthase (iNOS) gene and protein expression quantitatively in primary epithelial cells from very young children with cystic fibrosis (CF). Low levels of exhaled nitric oxide (NO) in CF suggest dysregulation of NO production in the airway. Due to the importance of NO in cell homeostasis and innate immunity, any defect in the pathway associated with CF would be a potential target for treatment. Methods: Cells were obtained by tracheobronchial brushing from 40 children with CF of mean (SD) age 2.1 (1.5) years and from 12 healthy non-atopic children aged 3.4 (1.2) years. Expression of iNOS mRNA was measured using quantitative PCR and iNOS protein by immunofluorescence and Western blot analysis. Results: Inducible NOS mRNA expression was significantly lower in CF patients with and without bacterial infection than in healthy children (0.22 and 0.23 v 0.76; p = 0.002 and p = 0.01, respectively). Low levels of iNOS gene expression were accompanied by low levels of iNOS protein expression as detected by Western blot analysis. Conclusions: These results support the findings of previous studies in adult patients with advanced disease, cell lines, and animal models. Our findings reflect the situation in children with mild lung disease. They indicate that low iNOS expression may be an innate defect in CF with potential consequences for local antimicrobial defence and epithelial cell function and provide evidence for an approach to treatment based on increasing epithelial NO production or the sensitivity of NO dependent cellular processes. |
| first_indexed | 2025-11-14T11:08:45Z |
| format | Journal Article |
| id | curtin-20.500.11937-76828 |
| institution | Curtin University Malaysia |
| institution_category | Local University |
| language | English |
| last_indexed | 2025-11-14T11:08:45Z |
| publishDate | 2006 |
| publisher | B M J PUBLISHING GROUP |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | curtin-20.500.11937-768282019-11-12T08:21:24Z Inducible NO synthase expression is low in airway epithelium from young children with cystic fibrosis Moeller, A. Horak, F. Lane, C. Knight, D. Kicic, Anthony Brennan, S. Franklin, P. Terpolilli, J. Wildhaber, J.H. Stick, S.M. Science & Technology Life Sciences & Biomedicine Respiratory System NITRIC-OXIDE SYNTHASE PSEUDOMONAS-AERUGINOSA INFECTION PULMONARY INFECTION LUNG-DISEASE CELLS INFANTS INFLAMMATION PATHWAY ASTHMA BREATH Background: This is the first study to measure inducible nitric oxide synthase (iNOS) gene and protein expression quantitatively in primary epithelial cells from very young children with cystic fibrosis (CF). Low levels of exhaled nitric oxide (NO) in CF suggest dysregulation of NO production in the airway. Due to the importance of NO in cell homeostasis and innate immunity, any defect in the pathway associated with CF would be a potential target for treatment. Methods: Cells were obtained by tracheobronchial brushing from 40 children with CF of mean (SD) age 2.1 (1.5) years and from 12 healthy non-atopic children aged 3.4 (1.2) years. Expression of iNOS mRNA was measured using quantitative PCR and iNOS protein by immunofluorescence and Western blot analysis. Results: Inducible NOS mRNA expression was significantly lower in CF patients with and without bacterial infection than in healthy children (0.22 and 0.23 v 0.76; p = 0.002 and p = 0.01, respectively). Low levels of iNOS gene expression were accompanied by low levels of iNOS protein expression as detected by Western blot analysis. Conclusions: These results support the findings of previous studies in adult patients with advanced disease, cell lines, and animal models. Our findings reflect the situation in children with mild lung disease. They indicate that low iNOS expression may be an innate defect in CF with potential consequences for local antimicrobial defence and epithelial cell function and provide evidence for an approach to treatment based on increasing epithelial NO production or the sensitivity of NO dependent cellular processes. 2006 Journal Article http://hdl.handle.net/20.500.11937/76828 10.1136/thx.2005.054643 English B M J PUBLISHING GROUP restricted |
| spellingShingle | Science & Technology Life Sciences & Biomedicine Respiratory System NITRIC-OXIDE SYNTHASE PSEUDOMONAS-AERUGINOSA INFECTION PULMONARY INFECTION LUNG-DISEASE CELLS INFANTS INFLAMMATION PATHWAY ASTHMA BREATH Moeller, A. Horak, F. Lane, C. Knight, D. Kicic, Anthony Brennan, S. Franklin, P. Terpolilli, J. Wildhaber, J.H. Stick, S.M. Inducible NO synthase expression is low in airway epithelium from young children with cystic fibrosis |
| title | Inducible NO synthase expression is low in airway epithelium from young children with cystic fibrosis |
| title_full | Inducible NO synthase expression is low in airway epithelium from young children with cystic fibrosis |
| title_fullStr | Inducible NO synthase expression is low in airway epithelium from young children with cystic fibrosis |
| title_full_unstemmed | Inducible NO synthase expression is low in airway epithelium from young children with cystic fibrosis |
| title_short | Inducible NO synthase expression is low in airway epithelium from young children with cystic fibrosis |
| title_sort | inducible no synthase expression is low in airway epithelium from young children with cystic fibrosis |
| topic | Science & Technology Life Sciences & Biomedicine Respiratory System NITRIC-OXIDE SYNTHASE PSEUDOMONAS-AERUGINOSA INFECTION PULMONARY INFECTION LUNG-DISEASE CELLS INFANTS INFLAMMATION PATHWAY ASTHMA BREATH |
| url | http://hdl.handle.net/20.500.11937/76828 |