文摘
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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
<p>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
<p>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
<p>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
<p>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.
