Regulation of Th2 cytokine genes by p38 MAPK-mediated phosphorylation of GATA-3

Kittipong Maneechotesuwan, Yao Xin, Kazuhiro Ito, Elen Jazrawi, Kang Yun Lee, Omar S. Usmani, Peter J. Barnes, Ian M. Adcock

Research output: Contribution to journalArticle

115 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)2491-2498
Number of pages8
JournalJournal of Immunology
Volume178
Issue number4
Publication statusPublished - Feb 15 2007
Externally publishedYes

Fingerprint

p38 Mitogen-Activated Protein Kinases
Phosphorylation
Cytokines
T-Lymphocytes
Karyopherins
Genes
Interleukin-13
Chromatin Immunoprecipitation
Interleukin-5
Nuclear Proteins
Genetic Promoter Regions
Interleukin-4
Allergens
Serine
Small Interfering RNA
Cytoplasm
Lymphocytes
Cell Line

ASJC Scopus subject areas

  • Immunology

Cite this

Maneechotesuwan, K., Xin, Y., Ito, K., Jazrawi, E., Lee, K. Y., Usmani, O. S., ... Adcock, I. M. (2007). Regulation of Th2 cytokine genes by p38 MAPK-mediated phosphorylation of GATA-3. Journal of Immunology, 178(4), 2491-2498.

Regulation of Th2 cytokine genes by p38 MAPK-mediated phosphorylation of GATA-3. / Maneechotesuwan, Kittipong; Xin, Yao; Ito, Kazuhiro; Jazrawi, Elen; Lee, Kang Yun; Usmani, Omar S.; Barnes, Peter J.; Adcock, Ian M.

In: Journal of Immunology, Vol. 178, No. 4, 15.02.2007, p. 2491-2498.

Research output: Contribution to journalArticle

Maneechotesuwan, K, Xin, Y, Ito, K, Jazrawi, E, Lee, KY, Usmani, OS, Barnes, PJ & Adcock, IM 2007, 'Regulation of Th2 cytokine genes by p38 MAPK-mediated phosphorylation of GATA-3', Journal of Immunology, vol. 178, no. 4, pp. 2491-2498.
Maneechotesuwan K, Xin Y, Ito K, Jazrawi E, Lee KY, Usmani OS et al. Regulation of Th2 cytokine genes by p38 MAPK-mediated phosphorylation of GATA-3. Journal of Immunology. 2007 Feb 15;178(4):2491-2498.
Maneechotesuwan, Kittipong ; Xin, Yao ; Ito, Kazuhiro ; Jazrawi, Elen ; Lee, Kang Yun ; Usmani, Omar S. ; Barnes, Peter J. ; Adcock, Ian M. / Regulation of Th2 cytokine genes by p38 MAPK-mediated phosphorylation of GATA-3. In: Journal of Immunology. 2007 ; Vol. 178, No. 4. pp. 2491-2498.
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