title: Poly (ADP-ribose) polymerase 14 and its enzyme activity regulates T(H)2 differentiation and allergic airway disease.
abstract: BACKGROUND
  IL-4 and signal transducer and activator of transcription 6 (STAT6) play an important role in the progression of allergic airway disease (AAD) or asthma. IL-4 and STAT6 mediate T(H)2 responses in T cells and immunoglobulin class-switching to IgE in B cells. Both T(H)2 responses and IgE promote the asthmatic condition. We have previously demonstrated that poly (ADP-ribose) polymerase (PARP) 14, a member of the PARP family of proteins, regulates the transcription function of STAT6. However, the role of PARP-14 in AAD is not known.
  
  
  OBJECTIVE
  Here we investigate the role of PARP-14 and the enzyme activity associated with it in a model of AAD dependent on airway hyperresponsiveness and lung inflammation. We also elucidate the mechanism by which PARP-14 regulates AAD.
  
  
  METHODS
  The role of PARP-14 and its enzyme activity in AAD and T(H)2 differentiation were examined by using a murine model of AAD and in vitro T(H) cell differentiation.
  
  
  RESULTS
  PARP-14-deficient animals show reduced lung pathology and IgE levels when compared with control animals. Treating mice with a pharmacologic inhibitor for PARP activity reduced the severity of airway hyperresponsiveness and lung inflammation. Mechanistically, our data indicate that PARP-14 and its enzyme activity aid in the differentiation of T cells toward a T(H)2 phenotype by regulating the binding of STAT6 to the Gata3 promoter.
  
  
  CONCLUSIONS
  PARP-14 and the catalytic activity associated with it promote T(H)2 differentiation and AAD in a murine model, and targeting PARP-14 might be a potential new therapy for allergic asthma.
authors: HB Wells Center for Pediatric Research and the Department of Pediatrics, Indiana University School of Medicine, Indianapolis, Ind, USA.
authors: Purvi
authors: P
authors: Mehrotra
authors: Andrew
authors: A
authors: Hollenbeck
authors: Jonathan P
authors: JP
authors: Riley
authors: Fang
authors: F
authors: Li
authors: Ravi J
authors: RJ
authors: Patel
authors: Nahid
authors: N
authors: Akhtar
authors: Shreevrat
authors: S
authors: Goenka
mesh_terms: D000818:Animals; D001249:Asthma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D016535:Bronchial Hyperreactivity / Q000201:enzymology / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002454:Cell Differentiation / Q000276:immunology; D002478:Cells, Cultured; D050990:GATA3 Transcription Factor / Q000235:genetics / Q000378:metabolism; D006967:Hypersensitivity / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D007073:Immunoglobulin E / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D011065:Poly(ADP-ribose) Polymerases / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000235:genetics; D012140:Respiratory Tract Diseases / Q000201:enzymology / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D050800:STAT6 Transcription Factor / Q000235:genetics / Q000378:metabolism; D018418:Th2 Cells / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology*
chemical_list: D050990:GATA3 Transcription Factor; C494748:Gata3 protein, mouse; D050800:STAT6 Transcription Factor; C494100:Stat6 protein, mouse; D007073:Immunoglobulin E; C522628:Parp14 protein, mouse; D011065:Poly(ADP-ribose) Polymerases