Amphiregulin expression in human mast cells and its effect on the primary human lung fibroblasts

Background: Amphiregulin is a member of the epidermal growth factor family and has been shown to stimulate the proliferation of human keratinocytes in an autocrine manner. Objective: The aim of the present study was to examine the expression change of growth factors, especially amphiregulin, in human mast cells induced by IgE cross-linking. Methods: Microarray analysis and RT-PCR were used to analyze the gene expression profile of human cord blood-derived mast cells (CBMCs) stimulated with IgE cross-linking. Protein secretion in the supernatants of CBMCs was measured by means of ELISA. Double-immunofluorescence staining was used to analyze the expression in the lung mast cells. Results: Of the 64 different growth factor genes analyzed, 5 were found to be substantially upregulated. Among them, amphiregulin mRNA was induced by 44-fold in CBMCs on activation through IgE cross-linking. Secretion of amphiregulin protein was evident in CBMCs 8 hours after stimulation. Amphiregulin was also expressed in human lung mast cells from patients with asthma, as demonstrated by means of double-immunofluorescence staining. Amphiregulin promoted the proliferation of the primary human lung fibroblasts, and amphiregulin-treated primary human lung fibroblasts showed a marked increase in the expression of c-fos, a proto-oncogene that facilitates or is required for the proliferation of a wide variety of cells. Conclusion: Human CBMCs secreted amphiregulin on IgE cross-linking, and the amphiregulin induced proliferation of primary human lung fibroblasts. These data suggest that local release of amphiregulin by human mast cells could play an important role in lung fibrosis by promoting the proliferation of primary human lung fibroblasts.