Abstract
BackgroundIn 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 (FcεRI).ResultsOne to two hours after FcεRI-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.ConclusionOur initial analysis of the transcriptional program induced in in vitro-derived human mast cells stimulated via the FcεRI 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 FcεRI 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.
Highlights
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
One of the many transcripts we found to be substantially induced in human mast cells stimulated via FcεRI was that for IL-11, a pleiotropic cytokine that has been implicated in airway inflammation and remodeling [11–13]; mast cells stimulated via the FcεRI secreted IL-11 protein
FcεRI-dependent activation of human mast cells results in substantially altered expression of over 2,400 genes The two mast cell preparations shown in Fig. 1 released 56.6 ± 4.1 or 63.0 ± 1.8% of their total histamine content by 1 h after anti-IgE stimulation, which is a strong secretory response in this mast cell type [15]
Summary
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. One of the many transcripts we found to be substantially induced in human mast cells stimulated via FcεRI was that for IL-11, a pleiotropic cytokine that has been implicated in airway inflammation and remodeling [11–13]; mast cells stimulated via the FcεRI secreted IL-11 protein These results indicate that analysis of the transcriptional profile of human mast cells stimulated by aggregation of FcεRI may be useful in suggesting new potential therapeutic targets in asthma and other IgE-associated allergic disorders
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