Transcriptional response of human mast cells stimulated via the FcεRI and identification of mast cells as a source of IL-11

One 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.Our 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.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 [1,2], as well as to produce certain cytokines and chemokines [1-4]. To search for new mast cell products, we used cDNA microarrays to analyze the transcriptional program in highly pure populations of human mast cells that had been stimulated via the FcεRI. While others have analyzed transcriptional profiles in certain rodent or human mast cell populations using microarray-based or alternative approaches [6-10], the transcriptional profile of human mast cells stimulated via the FcεRI has not yet been reported.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