Poly (ADP-ribose) polymerase 14 and its enzyme activity regulates TH2 differentiation and allergic airway disease - 30/01/13
Corresponding author: Shreevrat Goenka, PhD, passed away while this article was in press. For correspondence please contact Dr Mark H. Kaplan.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 TH2 responses in T cells and immunoglobulin class-switching to IgE in B cells. Both TH2 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 TH2 differentiation were examined by using a murine model of AAD and in vitro TH 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 TH2 phenotype by regulating the binding of STAT6 to the Gata3 promoter.
Conclusion |
PARP-14 and the catalytic activity associated with it promote TH2 differentiation and AAD in a murine model, and targeting PARP-14 might be a potential new therapy for allergic asthma.
Le texte complet de cet article est disponible en PDF.Key words : IL-4, signal transducer and activator of transcription 6, poly (ADP-ribose) polymerase 14, TH2 cells, Gata3, lung inflammation, airway hyperresponsiveness, poly (ADP-ribose) polymerase inhibitor, allergic airway disease
Abbreviations used : AAD, AHR, BAL, ChIP, H&E, NSNC, OVA, PARP, PAS, qPCR, SC, siRNA, STAT6, WT
Plan
| Supported by National Institutes of Health grant HL093105 and a Showalter Foundation grant. |
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| Disclosure of potential conflict of interest: S. Goenka has received research support, travel support, and payment for writing/reviewing from the National Institutes of Health/National Heart, Lung, and Blood Institute, and has received provision of writing assistance from the Indiana University School of Medicine. The rest of the authors declare that they have no relevant conflicts of interest. |
Vol 131 - N° 2
P. 521 - février 2013 Retour au numéro
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