Publication: Regulation of Th2 cytokine genes by p38 MAPK-mediated phosphorylation of GATA-3
Issued Date
2007-02-15
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ISSN
00221767
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2-s2.0-33846935457
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Mahidol University
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SCOPUS
Bibliographic Citation
Journal of Immunology. Vol.178, No.4 (2007), 2491-2498
Suggested Citation
Kittipong Maneechotesuwan, Yao Xin, Kazuhiro Ito, Elen Jazrawi, Kang Yun Lee, Omar S. Usmani, Peter J. Barnes, Ian M. Adcock Regulation of Th2 cytokine genes by p38 MAPK-mediated phosphorylation of GATA-3. Journal of Immunology. Vol.178, No.4 (2007), 2491-2498. doi:10.4049/jimmunol.178.4.2491 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/24578
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Title
Regulation of Th2 cytokine genes by p38 MAPK-mediated phosphorylation of GATA-3
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Abstract
GATA-3 plays a critical role in allergic diseases by regulating the release of cytokines from Th2 lymphocytes. However, the molecular mechanisms involved in the regulation of GATA-3 in human T lymphocytes are not yet understood. Using small interfering RNA to knock down GATA-3, we have demonstrated its critical role in regulating IL-4, IL-5, and IL-13 release from a human T cell line. Specific stimulation of T lymphocytes by costimulation of CD3 and CD28 to mimic activation by APCs induces translocation of GATA-3 from the cytoplasm to the nucleus, with binding to the promoter region of Th2 cytokine genes, as determined by chromatin immunoprecipitation. GATA-3 nuclear translocation is dependent on its phosphorylation on serine residues by p38 MAPK, which facilitates interaction with the nuclear transporter protein importin-α. This provides a means whereby allergen exposure leads to the expression of Th2 cytokines, and this novel mechanism may provide new approaches to treating allergic diseases. Copyright © 2007 by The American Association of Immunologists, Inc.