Poly (ADP-ribose) polymerase 14 and its enzyme activity regulates T(H)2 differentiation and allergic airway disease.
Poly (ADP-ribose) polymerase 14 and its enzyme activity regulates T(H)2 differentiation and allergic airway disease.
复制标题
DOI：
10.1016/j.jaci.2012.06.015
复制
发表时间：
2013-02
影响因子：
14.2
通讯作者：
Goenka, Shreevrat
中科院分区：
文献类型：
--
作者：
Mehrotra, Purvi;Hollenbeck, Andrew;Riley, Jonathan P.;Li, Fang;Patel, Ravi J.;Akhtar, Nahid;Goenka, Shreevrat
关键词：
Interleukin-4 (IL-4) and STAT6 play an important role in progression of allergic airway disease (AAD) or asthma. IL-4 and STAT6 mediate T helper 2 (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 PARP-14, a member of the poly ADP-ribose polymerase (PARP) family of proteins regulates the transcription function of STAT6. However, the role of PARP-14 in AAD is not known. Here we investigate the role of PARP-14 and the enzyme activity associated with it in AAD dependent on airway hyper-responsiveness (AHR) and lung inflammation. We also elucidate the mechanism by which PARP-14 regulates AAD. The role of PARP-14 and its enzyme activity in AAD and Th2 differentiation were examined using a mouse model of AAD and in vitro T helper cell differentiation. PARP-14 deficient animals when compared to controls show reduced lung pathology and IgE. Treating mice with a pharmacological inhibitor for PARP activity reduced the severity of AHR and lung inflammation. Mechanistically, our data indicate that PARP-14 and its enzyme activity aid in the differentiation of T cells towards a Th2 phenotype by regulating the binding of STAT6 to the Gata3 promoter. PARP-14 and the catalytic activity associated with it promote Th2 differentiation and AAD in a murine model, and targeting PARP-14 may be a potential new therapy for allergic asthma.
登录
查看更多内容
影响因子：
32.4
作者：
Stritesky GL;Muthukrishnan R;Sehra S;Goswami R;Pham D;Travers J;Nguyen ET;Levy DE;Kaplan MH
通讯作者：
Kaplan MH
影响因子：
14.2
作者：
Broide, David H.;Finkelman, Fred;Rothenberg, Marc E.
通讯作者：
Rothenberg, Marc E.
影响因子：
64.5
作者：
Zheng, WP;Flavell, RA
通讯作者：
Flavell, RA
影响因子：
4.8
作者：
Goenka, Shreevrat;Cho, Sung Hoon;Boothby, Mark
通讯作者：
Boothby, Mark
DOI：
10.1084/jem.187.6.939
发表时间：
1998-03-16
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Kuperman D;Schofield B;Wills-Karp M;Grusby MJ
通讯作者：
Grusby MJ