Role of stem cell factor and monocyte chemoattractant protein-1 in the interaction between fibroblasts and mast cells in fibrosis

Mast cell infiltration and accumulation is known to occur in tissue fibrosi s. Increased numbers of mast cells are detected in scleroderma or hypertrop hic scar skin, however, neither the role of mast cells nor the interaction of fibroblasts and mast cells in fibrosis are fully understood. A growing b ody of evidence indicate that mast cells are rich source of cytokines, grow th factors or chemokines, which are suggested to play an important role in the induction of fibrosis. Recent in vivo and in vitro studies suggest the involvement of monocyte chemoattractant protein-1 (MCP-1), a member of the C-C chemokine family, in fibrosis. Here, we examined the effect of stem cel l factor (SCF), a mast cell growth factor, on MCP-1 gene expression in a hu man mast cell line, HMC-1, and as well as the effect of MCP-1 on alpha1(I) collagen gene expression in human skin fibroblasts. HMC-1 cells spontaneous ly expressed MCP-1 mRNA transcripts, which was detectable by in situ hybrid ization and Northern blot analysis. Stimulation with SCF further upregulate d MCP-1 mRNA expression in a time- and dose-dependent manner, and stimulati on with 100 ng/ml SCF for 24 h induced a 3-fold increase of MCP-1 mRNA expr ession in HMC-1 cells as compared with unstimulated cells. The concentratio n of MCP-1 protein in the culture supernatants of 50 ng/ml SCF-stimulated H MC-1 cells (3816 +/- 70 pg/ml) was significantly elevated compared to unsti mulated cells (2588 +/- 130 pg/ml) (P < 0.01), as assessed by ELISA. Advers ely, MCP-1 induced <alpha>1(I) collagen mRNA expression in normal skin fibr oblasts dose-dependently. Finally, comparative study revealed that the conc entration of SCF in the culture supernatants of scleroderma fibroblasts at primary passages was significantly increased (344.6 +/- 182.4 pg/ml), as co mpared with normal skin fibroblasts (72.4 +/- 20.2 pg/ml) (P < 0.05). These results suggest that fibroblast-derived SCF upregulates MCP-1 expression a nd synthesis in mast cells, which acts on fibroblasts to enhance al(I) coll agen mRNA expression. Our data may indicate an important interaction of fib roblasts and mast cells, via SCF and MCP-1, in the induction of fibrosis. ( C) 2001 Elsevier Science Ireland Ltd. All rights reserved.