Evaluation of genome-wide expression profiles of blood and sputum neutrophils in cystic fibrosis patients before and after antibiotic therapy.
In seeking more specific biomarkers of the cystic fibrosis (CF) lung inflammatory disease that would be sensitive to antibiotic therapy, we sought to evaluate the gene expression profiles of neutrophils in CF patients before treatment in comparison with non-CF healthy individuals and after antibioti...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2014-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC4118979?pdf=render |
| _version_ | 1828320037803393024 |
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| author | Massimo Conese Stefano Castellani Silvia Lepore Orazio Palumbo Antonio Manca Teresa Santostasi Angela Maria Polizzi Massimiliano Copetti Sante Di Gioia Valeria Casavola Lorenzo Guerra Anna Diana Pasqualina Montemurro Maria Addolorata Mariggiò Crescenzio Gallo Angela Bruna Maffione Massimo Carella |
| author_facet | Massimo Conese Stefano Castellani Silvia Lepore Orazio Palumbo Antonio Manca Teresa Santostasi Angela Maria Polizzi Massimiliano Copetti Sante Di Gioia Valeria Casavola Lorenzo Guerra Anna Diana Pasqualina Montemurro Maria Addolorata Mariggiò Crescenzio Gallo Angela Bruna Maffione Massimo Carella |
| author_sort | Massimo Conese |
| collection | DOAJ |
| description | In seeking more specific biomarkers of the cystic fibrosis (CF) lung inflammatory disease that would be sensitive to antibiotic therapy, we sought to evaluate the gene expression profiles of neutrophils in CF patients before treatment in comparison with non-CF healthy individuals and after antibiotic treatment. Genes involved in neutrophil-mediated inflammation, i.e. chemotaxis, respiratory burst, apoptosis, and granule exocytosis, were the targets of this study. Microarray analysis was carried out in blood and airway neutrophils from CF patients and in control subjects. A fold change (log) threshold of 1.4 and a cut-off of p<0.05 were utilized to identify significant genes. Community networks and principal component analysis were used to distinguish the groups of controls, pre- and post-therapy patients. Control subjects and CF patients before therapy were readily separated, whereas a clear distinction between patients before and after antibiotic therapy was not possible. Blood neutrophils before therapy presented 269 genes down-regulated and 56 up-regulated as compared with control subjects. Comparison between the same patients before and after therapy showed instead 44 genes down-regulated and 72 up-regulated. Three genes appeared to be sensitive to therapy and returned to "healthy" condition: phorbol-12-myristate-13-acetate-induced protein 1 (PMAIP1), hydrogen voltage-gated channel 1 (HVCN1), and β-arrestin 1 (ARRB1). The up-regulation of these genes after therapy were confirmed by real time PCR. In airway neutrophils, 1029 genes were differentially expressed post- vs pre-therapy. Of these, 30 genes were up-regulated and 75 down-regulated following antibiotic treatment. However, biological plausibility determined that only down-regulated genes belonged to the gene classes studied for blood neutrophils. Finally, it was observed that commonly expressed genes showed a greater variability in airway neutrophils than that found in blood neutrophils, both before and after therapy. These results indicate more specific targets for future interventions in CF patients involving respiratory burst, apoptosis, and granule exocytosis. |
| first_indexed | 2024-04-13T18:05:59Z |
| format | Article |
| id | doaj.art-ee236adcb874467382314450b319bf1c |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-13T18:05:59Z |
| publishDate | 2014-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-ee236adcb874467382314450b319bf1c2022-12-22T02:36:05ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0198e10408010.1371/journal.pone.0104080Evaluation of genome-wide expression profiles of blood and sputum neutrophils in cystic fibrosis patients before and after antibiotic therapy.Massimo ConeseStefano CastellaniSilvia LeporeOrazio PalumboAntonio MancaTeresa SantostasiAngela Maria PolizziMassimiliano CopettiSante Di GioiaValeria CasavolaLorenzo GuerraAnna DianaPasqualina MontemurroMaria Addolorata MariggiòCrescenzio GalloAngela Bruna MaffioneMassimo CarellaIn seeking more specific biomarkers of the cystic fibrosis (CF) lung inflammatory disease that would be sensitive to antibiotic therapy, we sought to evaluate the gene expression profiles of neutrophils in CF patients before treatment in comparison with non-CF healthy individuals and after antibiotic treatment. Genes involved in neutrophil-mediated inflammation, i.e. chemotaxis, respiratory burst, apoptosis, and granule exocytosis, were the targets of this study. Microarray analysis was carried out in blood and airway neutrophils from CF patients and in control subjects. A fold change (log) threshold of 1.4 and a cut-off of p<0.05 were utilized to identify significant genes. Community networks and principal component analysis were used to distinguish the groups of controls, pre- and post-therapy patients. Control subjects and CF patients before therapy were readily separated, whereas a clear distinction between patients before and after antibiotic therapy was not possible. Blood neutrophils before therapy presented 269 genes down-regulated and 56 up-regulated as compared with control subjects. Comparison between the same patients before and after therapy showed instead 44 genes down-regulated and 72 up-regulated. Three genes appeared to be sensitive to therapy and returned to "healthy" condition: phorbol-12-myristate-13-acetate-induced protein 1 (PMAIP1), hydrogen voltage-gated channel 1 (HVCN1), and β-arrestin 1 (ARRB1). The up-regulation of these genes after therapy were confirmed by real time PCR. In airway neutrophils, 1029 genes were differentially expressed post- vs pre-therapy. Of these, 30 genes were up-regulated and 75 down-regulated following antibiotic treatment. However, biological plausibility determined that only down-regulated genes belonged to the gene classes studied for blood neutrophils. Finally, it was observed that commonly expressed genes showed a greater variability in airway neutrophils than that found in blood neutrophils, both before and after therapy. These results indicate more specific targets for future interventions in CF patients involving respiratory burst, apoptosis, and granule exocytosis.http://europepmc.org/articles/PMC4118979?pdf=render |
| spellingShingle | Massimo Conese Stefano Castellani Silvia Lepore Orazio Palumbo Antonio Manca Teresa Santostasi Angela Maria Polizzi Massimiliano Copetti Sante Di Gioia Valeria Casavola Lorenzo Guerra Anna Diana Pasqualina Montemurro Maria Addolorata Mariggiò Crescenzio Gallo Angela Bruna Maffione Massimo Carella Evaluation of genome-wide expression profiles of blood and sputum neutrophils in cystic fibrosis patients before and after antibiotic therapy. PLoS ONE |
| title | Evaluation of genome-wide expression profiles of blood and sputum neutrophils in cystic fibrosis patients before and after antibiotic therapy. |
| title_full | Evaluation of genome-wide expression profiles of blood and sputum neutrophils in cystic fibrosis patients before and after antibiotic therapy. |
| title_fullStr | Evaluation of genome-wide expression profiles of blood and sputum neutrophils in cystic fibrosis patients before and after antibiotic therapy. |
| title_full_unstemmed | Evaluation of genome-wide expression profiles of blood and sputum neutrophils in cystic fibrosis patients before and after antibiotic therapy. |
| title_short | Evaluation of genome-wide expression profiles of blood and sputum neutrophils in cystic fibrosis patients before and after antibiotic therapy. |
| title_sort | evaluation of genome wide expression profiles of blood and sputum neutrophils in cystic fibrosis patients before and after antibiotic therapy |
| url | http://europepmc.org/articles/PMC4118979?pdf=render |
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