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

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.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11586/103891
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