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BACKGROUND Mast cells frequently accumulate at the site of fibrosis and their contribution has been suspected in the pathogenesis of fibrotic conditions. However, it still remains unknown whether human mast cells synthesize transforming growth factor beta1 (TGF-beta1). OBJECTIVE We have investigated whether cord blood-derived human cultured mast cells express messenger RNA (mRNA) for TGF-beta and produce bioactive TGF-beta1. METHODS Mast cells were obtained by culturing mononuclear cells from cord blood in the presence of stem cell factor and interleukin-6. Expression of mRNA for TGF-beta1 was examined by the method of reverse transcriptase-polymerase chain reaction (RT-PCR). Immunocytochemical staining for TGF-beta and growth-inhibitory assay using Mv1Lu cells were also performed. RESULTS The cultured human mast cells constitutively expressed mRNA for TGF-beta1. With calcium ionophore A23187, the intensity of the PCR-amplified band for TGF-beta1 was not increased. Immunocytochemical staining showed that the cultured mast cells were positive for both latency-associated peptide and activated forms of TGF-beta. Bioassay with Mv1Lu cells and R 4-2 mutant cells showed that mast-cell conditioned medium had a bioactivity of TGF-beta1. CONCLUSIONS Cord blood-derived human cultured mast cells constitutively express mRNA for TGF-beta1 and produce functional TGF-beta1. Because TGF-beta1 has been shown to be highly fibrogenic, these results may highlight a novel role for human mast cells in tissue fibrosis.
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