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J Biol Chem, Vol. 274, Issue 18, 12910-12916, April 30, 1999

Regulation of the Human Interleukin-5 Promoter by Ets Transcription Factors
ETS1 AND ETS2, BUT NOT ELF-1, COOPERATE WITH GATA3 AND HTLV-I TAX1

Sibylle G. BlumenthalDagger , Gabriele AicheleDagger , Thomas Wirth§, Armin P. Czernilofsky, Alfred NordheimDagger , and Jürgen DittmerDagger

From the Dagger  Institut für Zellbiologie, Abteilung Molekularbiologie, Universität Tübingen, Auf der Morgenstelle 15, 72076 Tübingen, Germany, the § Institut für Medizinische Strahlenkunde und Zellforschung (MSZ), Versbacher Strasse 5, 97078 Würzburg, Germany, and the  Bender + Co Gesellschaft mbH, Dr. Boehringer-Gasse 5-11, 1121 Wien, Austria

Interleukin-5 (IL-5), expressed primarily by type-2 T helper (Th2) cells, plays an important role in the development of allergic diseases, such as allergic asthma. Studying the regulation of IL-5 gene expression by Ets transcription factors, we found that Ets1 and Ets2, but not Elf-1, were able to activate the human IL-5 promoter in Jurkat T-cells. This required the presence of either phorbol 12-myristate acetate (PMA) plus ionomycin or PMA plus the viral protein HTLV-I Tax1. By mutation studies, it could be shown that Ets1 and Ets2 exerted their effects on the IL-5 promoter through a GGAA motif within the Cle0 element. In myeloid Kasumi cells, Ets1 and Ets2 failed to stimulate IL-5 promoter activity, unless the T-cell specific transcription factor GATA3 was added. These results show, for the first time, that Ets1 and Ets2 are able to cooperate with GATA3. Both ionomycin and Tax1 increased the combined effect of GATA3 with Ets1 and Ets2 in the presence of PMA. The data further demonstrate that, in addition to Ets1, Ets2 is also able to functionally cooperate with Tax1. The synergism of GATA3 with either Ets1 or Ets2 may play an important role in calcium- or Tax1-dependent regulation of IL-5 expression in Th2 cells or in HTLV-I transformed adult T-cell leukemia cells, respectively.


Copyright © 1999 by The American Society for Biochemistry and Molecular Biology, Inc.
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