FcεRI-dependent gene expression in human mast cells is differentially controlled by T helper type 2 cytokines - 29/08/11
Reprint requests: Joshua A. Boyce, MD, Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Smith Research Building, 1 Jimmy Fund Way, Boston, MA 02115Abstract |
Background |
Mast cells (MCs) proliferate in response to TH2 cytokines and express genes de novo after activation. Limited information is available concerning the interplay between these events.
Objective |
We explored the potential for TH2 cytokines to alter activation-dependent gene expression by MCs.
Methods |
Cord blood–derived human (h)MCs maintained in stem cell factor (SCF) alone were compared with replicates treated with IL-4, IL-5, or IL-9, respectively, for their patterns of FcεRI-dependent gene induction using microarray technology.
Results |
Activation of SCF-treated hMCs upregulated their expression of roughly 140 transcripts at 2 hours, including genes involved in cell cycle progression and arrest. Each cytokine substantially modified this profile; 
800 inducible genes apiece were controlled by IL-5 or IL-9, whereas 169 inducible genes were controlled by IL-4. IL-4 favored the induction of cytokines and of genes associated with cell growth arrest (GADD34, GAS-1, CIDE-A, INK4D, and BAX) and completely abolished the enhanced proliferation observed in the other 3 groups after activation. Conversely, IL-5 priming induced preferential upregulation of genes involved in cell proliferation and did not abolish thymidine incorporation.
Conclusions |
TH2 cytokines differentially modulate gene induction in hMCs after FcεRI cross-linkage. IL-4 uniquely controls cytokine gene expression by hMCs and might also limit their activation-driven proliferation.
Le texte complet de cet article est disponible en PDF.Keywords : cytokines, activation, mast cells, asthma
Abbreviations : FcεRI, hMC, MC, MAPK, SCF
Plan
 | Supported by National Institutes of Health grants AI-48802, AI-52353, AI-31599, and HL-36110, by a grant from the Charles Dana Foundation, by a grant from the Vinik Family Fund for Research in Allergic Diseases, and by a grant from the Hyde and Watson Foundation. Dr Price is the recipient of a grant from GlaxoSmithKline. Dr Bagga is funded by a grant from Millennium Pharmaceuticals. |
Vol 112 - N° 6
P. 1119-1126 - décembre 2003 Retour au numéro
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