p38 MAP kinase drives the expression of mast cell-derived IL-9 via activation of the transcription factor GATA-1.
Mast cells are able to produce a huge panel of mediators including the Th2-type cytokine IL-9, which is considered to be a key mediator for the pathogenesis of allergic asthma, but detailed information on the regulation of IL-9 transcription in mast cells has been scarce. Herein we provide evidence that the erythroid/myeloid transcription factor GATA-1, which is not expressed in Th2 cells, is a potent activator of IL-9 expression in murine bone marrow-derived mast cells (BMMC). Furthermore, in mast cells, but not in Th2 cells, production of IL-9 is sensitive to inhibition of p38 MAP kinase. As transactivation mediated by GATA-1 is also sensitive to inhibition of p38 MAP kinase, and GATA-1 is a target for p38 MAP kinase-mediated phosphorylation in vitro, we conclude that both signaling molecules represent a part of a mast cell-specific signaling network that regulates the expression of IL-9.
Stassen
Michael
M
Institute for Immunology, Johannes Gutenberg University, Mainz, Germany. stassenm@uni-mainz.de
Klein
Matthias
M
Becker
Marc
M
Bopp
Tobias
T
Neudörfl
Christine
C
Richter
Christoph
C
Heib
Valeska
V
Klein-Hessling
Stefan
S
Serfling
Edgar
E
Schild
Hansjörg
H
Schmitt
Edgar
E
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D005260:Female; D050982:GATA1 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D050989:GATA2 Transcription Factor / Q000235:genetics / Q000378:metabolism; D050990:GATA3 Transcription Factor / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D016906:Interleukin-9 / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008407:Mast Cells / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D009154:Mutation; D010766:Phosphorylation; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000378:metabolism; D018418:Th2 Cells / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
D050982:GATA1 Transcription Factor; D050989:GATA2 Transcription Factor; D050990:GATA3 Transcription Factor; D016906:Interleukin-9; D012333:RNA, Messenger; D048051:p38 Mitogen-Activated Protein Kinases