FcεRI-dependent gene expression in human mast cells is differentially controlled by T helper type 2 cytokines
| Autor: | Jose M. Lora, Jaclyn Sicoli, Michael J. Briskin, Kursteen S. Price, Joshua A. Boyce, Savita Bagga, Martin R. Hodge, Jose-Carlos Gutierrez-Ramos, Amal Al-Garawi, Michael D. Pickard |
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| Rok vydání: | 2003 |
| Předmět: |
Transcriptional Activation
medicine.medical_treatment Cellular differentiation Immunology Priming (immunology) Stem cell factor Receptors Fc Biology Th2 Cells Gene expression medicine Humans Immunology and Allergy Mast Cells Cells Cultured Oligonucleotide Array Sequence Analysis Regulation of gene expression Stem Cell Factor Cell growth Gene Expression Profiling Cell Differentiation Immunoglobulin E Fetal Blood Recombinant Proteins Cell biology Gene expression profiling Cytokine Gene Expression Regulation Cytokines |
| Zdroj: | Journal of Allergy and Clinical Immunology. 112:1119-1126 |
| ISSN: | 0091-6749 |
| Popis: | Background Mast cells (MCs) proliferate in response to T H 2 cytokines and express genes de novo after activation. Limited information is available concerning the interplay between these events. Objective We explored the potential for T H 2 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 FceRI-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 T H 2 cytokines differentially modulate gene induction in hMCs after FceRI cross-linkage. IL-4 uniquely controls cytokine gene expression by hMCs and might also limit their activation-driven proliferation. |
| Databáze: | OpenAIRE |
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