title: Transcriptional response of human mast cells stimulated via the Fc(epsilon)RI and identification of mast cells as a source of IL-11.
abstract: BACKGROUND
  In asthma and other allergic disorders, the activation of mast cells by IgE and antigen induces the cells to release histamine and other mediators of inflammation, as well as to produce certain cytokines and chemokines. To search for new mast cell products, we used complementary DNA microarrays to analyze gene expression in human umbilical cord blood-derived mast cells stimulated via the high-affinity IgE receptor (Fc(epsilon)RI).
  
  
  RESULTS
  One to two hours after Fc(epsilon)RI-dependent stimulation, more than 2,400 genes (about half of which are of unknown function) exhibited 2-200 fold changes in expression. The transcriptional program included changes in the expression of IL-11 and at least 30 other cytokines and chemokines. Human mast cells secreted 130-529 pg of IL-11/106 cells by 6 h after stimulation with anti-IgE.
  
  
  CONCLUSIONS
  Our initial analysis of the transcriptional program induced in in vitro-derived human mast cells stimulated via the Fc(epsilon)RI has identified many products that heretofore have not been associated with this cell type, but which may significantly influence mast cell function in IgE-associated host responses. We also have demonstrated that mast cells stimulated via the Fc(epsilon)RI can secrete IL-11. Based on the previously reported biological effects of IL-11, our results suggest that production of IL-11 may represent one link between IgE-dependent mast cell activation in subjects with allergic asthma and the development of a spectrum of structural changes in the airways of these individuals; such changes, collectively termed "airway remodeling," can constitute an important long term consequence of asthma.
authors.affiliation: Department of Pathology, Stanford University School of Medicine, Stanford, California, USA. aat99110@par.odn.ne.jp
authors.forename: Koichi
authors.initials: K
authors.lastname: Sayama
authors.forename: Maximilian
authors.initials: M
authors.lastname: Diehn
authors.forename: Kentaro
authors.initials: K
authors.lastname: Matsuda
authors.forename: Carolina
authors.initials: C
authors.lastname: Lunderius
authors.forename: Mindy
authors.initials: M
authors.lastname: Tsai
authors.forename: See-Ying
authors.initials: SY
authors.lastname: Tam
authors.forename: David
authors.initials: D
authors.lastname: Botstein
authors.forename: Patrick O
authors.initials: PO
authors.lastname: Brown
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Galli
mesh_terms: D000888:Antibodies, Anti-Idiotypic / Q000494:pharmacology; D002478:Cells, Cultured; D005786:Gene Expression Regulation / Q000187:drug effects; D006636:Histamine Release / Q000187:drug effects; D006801:Humans; D007073:Immunoglobulin E / Q000276:immunology; D017370:Interleukin-11 / Q000235:genetics* / Q000378:metabolism; D015847:Interleukin-4 / Q000494:pharmacology; D008407:Mast Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D017455:Receptors, IgE / Q000502:physiology*; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D000888:Antibodies, Anti-Idiotypic; D017370:Interleukin-11; D017455:Receptors, IgE; D015847:Interleukin-4; D007073:Immunoglobulin E