Background: Cystic fibrosis (CF) lung disease is characterized by massive extravasation of neutrophils into the airways that undergo apoptosis and thereby do not clear respiratory infections. The surrogate end-points that describe this process and the effect of antibiotic therapy, such as spirometry, are not sensitive and non- specific. We sought to evaluate the gene expression profile of circulating neutrophils in CF patients before and after antibiotic treatment. Methods: Microarray analysis (28,869 genes, Affymetrix GeneChip Gene 1.0 ST Array System) was performed in blood neutrophils from 10 CF patients before and after treatment for clinical exacerbation with antibiotics and 7 healthy control subjects. Results: Blood neutrophils before therapy presented 293 down-regulated genes and 57 up- regulated genes as compared with control subjects (considering as cut-off P < 0.05 by ANOVA). Comparison between the same patients before and after therapy (with the same cut-off by paired t test) showed instead that 1,422 genes were down- regulated and 282 up-regulated following antibiotic treatment. Interestingly, 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 dom-3 homolog Z (DOM3Z). The up-regulation of these genes after therapy were confirmed by RT -PCR in blood neutrophils (n=5) and in sputum neutrophils obtained from the same patients (n=7). Conclusions: These results suggest the feasibility of investigating novel biomarkers of therapeutic efficacy by a global gene-wide platform and indicate more specific targets for future interventions involving respiratory burst and apoptosis.
Evaluation of genome-wide expression profiles of blood neutrophils in cystic fibrosis patients before and after antibiotic therapy.
CASTELLANI S;MARIGGIO', Maria Addolorata;FUMARULO, Ruggiero;MONTEMURRO, Pasqualina;
2012-01-01
Abstract
Background: Cystic fibrosis (CF) lung disease is characterized by massive extravasation of neutrophils into the airways that undergo apoptosis and thereby do not clear respiratory infections. The surrogate end-points that describe this process and the effect of antibiotic therapy, such as spirometry, are not sensitive and non- specific. We sought to evaluate the gene expression profile of circulating neutrophils in CF patients before and after antibiotic treatment. Methods: Microarray analysis (28,869 genes, Affymetrix GeneChip Gene 1.0 ST Array System) was performed in blood neutrophils from 10 CF patients before and after treatment for clinical exacerbation with antibiotics and 7 healthy control subjects. Results: Blood neutrophils before therapy presented 293 down-regulated genes and 57 up- regulated genes as compared with control subjects (considering as cut-off P < 0.05 by ANOVA). Comparison between the same patients before and after therapy (with the same cut-off by paired t test) showed instead that 1,422 genes were down- regulated and 282 up-regulated following antibiotic treatment. Interestingly, 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 dom-3 homolog Z (DOM3Z). The up-regulation of these genes after therapy were confirmed by RT -PCR in blood neutrophils (n=5) and in sputum neutrophils obtained from the same patients (n=7). Conclusions: These results suggest the feasibility of investigating novel biomarkers of therapeutic efficacy by a global gene-wide platform and indicate more specific targets for future interventions involving respiratory burst and apoptosis.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
