Influence of IgE-mediated activation of cultured human mast cells on proliferation and type I collagen production by human dermal fibroblasts

Background: Mast cells have been suggested to be involved in fibrotic conditions, but it still remains unknown whether IgE-mediated activation of human mast cells promotes fibrogenesis by human fibroblasts. Objective: The purpose of this study was to determine whether IgE-mediated activation of cultured human mast cells can promote fibrogenesis by cultured human dermal fibroblasts. Methods: Mast cells derived from human umbilical cord blood cells were incubated with IgE and then activated by anti-IgE, and histamine release was measured. IgE-sensitized mast cells were cocultured with fibroblasts from normal dermis and activated with anti-IgE to induce histamine release, after which proliferation and type I collagen synthesis by the fibroblasts mere determined. Results: Coculture of subconfluent human dermal fibroblasts with IgE-sensitized mast cells did not affect fibroblast proliferation. However, fibroblast proliferation was increased by activated mast cells, and a significant increase was observed in the presence of 10(5) or 3 x 10(5) mast cells/mL. The promotion of fibroblast proliferation by mast cells (3 x 10(5)/mL) was partly inhibited by ketotifen at a concentration that significantly reduced histamine release from mast cells. On the other hand, IgE-mediated activation of mast cells did not increase type I collagen production by confluent human dermal fibroblasts. Conclusion: IgE-mediated activation of cultured human mast cells could increase the proliferation of human dermal fibroblasts, but did not promote type I collagen production by the fibroblasts under the conditions tested.