Poly (ADP-ribose) polymerase 14 and its enzyme activity regulates T(H)2 differentiation and allergic airway disease.
J Allergy Clin Immunol
; 131(2): 521-31.e1-12, 2013 Feb.
Article
in En
| MEDLINE
| ID: mdl-22841009
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.CONCLUSION:
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Respiratory Tract Diseases
/
Bronchial Hyperreactivity
/
Poly(ADP-ribose) Polymerases
/
Th2 Cells
/
Hypersensitivity
Type of study:
Prognostic_studies
Limits:
Animals
Language:
En
Journal:
J Allergy Clin Immunol
Year:
2013
Document type:
Article
Affiliation country:
United States