Production of fibrogenic cytokines by cord blood-derived cultured human mast cells.

Abstract

Mast cells are a potential source of cytokines, but their contribution to nonallergic inflammatory conditions, such as fibrosis, remains unclear. We investigated whether cord blood-derived cultured human mast cells could produce fibrogenic cytokines by IgE-mediated activation. Mast cells were obtained from human cord blood mononuclear cells by culture with stem cell factor and IL-6. The mast cells were incubated with human myeloma IgE and were activated with anti-IgE. The expression of messenger RNA for fibrogenic cytokines was examined by the reverse-transcription polymerase chain reaction, and cytokine protein was assayed by enzyme-linked immunosorbent assay, or bioassay. Cultured human mast cells constitutively expressed mRNA for transforming growth factor-beta(1), and its expression was not increased by anti-IgE stimulation. The cells released this factor into the culture medium spontaneously, which showed bioactivity after heat treatment. The mast cells also expressed mRNA for platelet-derived growth factor A, which was enhanced with a peak at 3 hours by stimulation with anti-IgE. Conditioned medium from nonactivated mast cells did not contain basic fibroblast growth factor, but this cytokine was released into the medium in a time-dependent manner after stimulation with anti-IgE. Human mast cells activated by IgE-mediated stimulation show production of fibrogenic cytokines that varies depending on the cytokine, which suggests possible involvement of mast cell cytokines in the development of fibrosis.