Effect of mast cell-derived mediators and mast cell-related neutral proteases on human dermal fibroblast proliferation and type I collagen production

Background: Possible involvement of mast cells in various fibrotic conditions has been suggested, hut the relative contribution of each mast cell mediator and neutral protease to fibroproliferative activity remains to be elucidated. Objective: We investigated the effect of mast cell-derived mediators and mast cell-related neutral proteases on type I collagen production and proliferation by human dermal fibroblasts. Methods: Mast cell-derived mediators or neutral proteases were added to cultured fibroblasts from normal dermis, and cell proliferation and type I collagen synthesis were assayed. Results: Fibroblast proliferation was increased by 2.8 x 10(-9) mol/L prostaglandin D-2 and 10 mu g/mL carboxypeptidase A, but not by leukotriene D-4 or cathepsin G at the concentrations studied. Proliferation was increased by tryptase in a concentration-dependent manner, and a significant increase was observed at concentrations of 1 and 10 mu g/mL. Production of type I collagen by fibroblasts was increased in the presence of 2.0 x 10(-9) mol/L leukotriene D-4 and 10 mu g/mL tryptase. Conclusion: Mast cell-derived mediators prostaglandin D-2 and Leukotriene D-4 and mast cell-related neutral proteases carboxypeptidase A and tryptase increase the proliferation and type I collagen production of human dermal fibroblasts in various manners.