title: FcepsilonRI-dependent gene expression in human mast cells is differentially controlled by T helper type 2 cytokines.
abstract: 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 FcepsilonRI-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; approximately 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 FcepsilonRI cross-linkage. IL-4 uniquely controls cytokine gene expression by hMCs and might also limit their activation-driven proliferation.
authors.affiliation: Department of Immunobiology and Inflammation, Cambridge, MA, USA.
authors.forename: José M
authors.initials: JM
authors.lastname: Lora
authors.forename: Amal
authors.initials: A
authors.lastname: Al-Garawi
authors.forename: Michael D
authors.initials: MD
authors.lastname: Pickard
authors.forename: Kursteen S
authors.initials: KS
authors.lastname: Price
authors.forename: Savita
authors.initials: S
authors.lastname: Bagga
authors.forename: Jaclyn
authors.initials: J
authors.lastname: Sicoli
authors.forename: Martin R
authors.initials: MR
authors.lastname: Hodge
authors.forename: José-Carlos
authors.initials: JC
authors.lastname: Gutiérrez-Ramos
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Briskin
authors.forename: Joshua A
authors.initials: JA
authors.lastname: Boyce
mesh_terms: D002454:Cell Differentiation; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology*; D005312:Fetal Blood; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D007073:Immunoglobulin E / Q000378:metabolism*; D008407:Mast Cells / Q000166:cytology* / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D011961:Receptors, Fc / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology; D019089:Stem Cell Factor / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology* / Q000378:metabolism; D015533:Transcriptional Activation
chemical_list: D016207:Cytokines; D011961:Receptors, Fc; D011994:Recombinant Proteins; D019089:Stem Cell Factor; D007073:Immunoglobulin E