2015, 2006, English, Article, Journal or magazine article edition: A role for Ets1, synergizing with AP-1 and GATA-3 in the regulation of IL-5 transcription in mouse Th2 lymphocytes Wang, Jun; Shannon, M Frances; Young, Ian

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Physical Description
  • journal article
Published
  • Oxford University Press, 2015-12-13T23:00:54Z 2006 2015-12-12T07:36:38Z
Language
  • English

Edition details

Title
  • A role for Ets1, synergizing with AP-1 and GATA-3 in the regulation of IL-5 transcription in mouse Th2 lymphocytes
Author
  • Wang, Jun
  • Shannon, M Frances
  • Young, Ian
Published
  • Oxford University Press, 2015-12-13T23:00:54Z 2006 2015-12-12T07:36:38Z
Physical Description
  • journal article
Part Of
  • International Immunology
Subjects
Summary
  • IL-5 is a key regulator of eosinophilic inflammation and is selectively expressed by antigen-activated Th2 lymphocytes. An important role for the proximal AP-1 and GATA sites in regulating IL-5 transcription is generally accepted but the significance of an adjacent Ets/​NFAT site has remained unclear. We have investigated its role using the mouse Th2 clone D10.G4.1. Transcription of IL-5 reporter gene plasmids could be induced in D10 cells by phorbol myristate acetate/​ cyclic adenosine monophosphate (PMA/​cAMP) stimulation and significantly further enhanced by activation of the mitogen-activated protein (MAP) kinase pathways. Strong induction of IL-5 mRNA was also induced by PMA/​ cAMP. Mutagenesis showed that the Ets/​NFAT site is of critical importance along with the AP-1 and GATA sites in regulating IL-5 transcription stimulated by PMA/​cAMP and MAP kinase activation. Transactivation was used to investigate the transcription factors which could function at the three sites and possible synergistic interactions. AP-1 (c-Fos/​c-Jun) strongly induced IL-5 transcription and dominant negative AP-1 constructs confirmed that AP-1 plays an important role in regulating IL-5 expression. Ets1, unlike other members of the Ets/​NFAT family, synergized strongly with AP-1 suggesting that Ets1 is the family member which functions at the Ets/​NFAT site. AP-1/​Ets1 transactivation also stimulated IL-5 mRNA expression. Ets1 binding to the proximal promoter region, demonstrated by chromatin immunoprecipitation, was stimulated by PMA/​cAMP. The absolute dependence on the binding sites for Ets1, AP-1 and GATA-3 together with the strong synergy between Ets1 and AP-1 suggest close cooperative interactions between the three transcription factors in the regulation of IL-5 expression in mouse T cells.
Language
  • English
Identifier
  • oai:openresearch-repository.anu.edu.au:1885/​84337
  • 10.1093/​intimm/​dxh370
  • oai:digitalcollections.anu.edu.au:1885/​84337
  • 0953-8178

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