Monocyte chemoattractant protein-1 production by human detrusor smooth muscle cells

Purpose: Most recently attention has turned to the secretory properties of smooth muscle cells. Monocyte chemoattractant protein-1 (MCP-1) is a potent chemokine that causes mast cells recruitment and provokes mast cells activation in vitro. We investigated whether MCP-1 is produced by human detrusor smooth muscle cells (HDSMCs) cultured under inflammatory conditions. Materials and Methods: Using an explantation technique HDSMCs were isolated and short-term cultured. HDSMCs were incubated at 37C for 24 hours with the proinflammatory mediators interleukin-1beta (IL-1beta), tumor necrosis factor (TNF-alpha), lipopolysaccharide, histamine, leukotriene D-4 and prostaglandin E-2. The level of MCP-1 in cell supernatants were measured by enzyme linked immunoassay. Results: There was basal secretion of MCP-1 in unstimulated cultures. Following 24-hour incubation with IL-1beta or TNF-alpha (1 pg/ml to 100 ng/ml) the level of MCP-1 increased in a dose dependent manner. IL-1beta was more potent at inducing MCP-1 release in 8 of 10 experiments. Lipopolysaccharide (10 Ag/ml), histamine (100 muM), leukotriene D-4 (50 nM), prostaglandin E-2 (1 AM) and KC1 (30 to 100 mM) failed to induce MCP-1 production. When IL-10 (10 ng/ml) and TNF-alpha (10 ng/ml) were given in combination, a highly synergistic effect on MCP-1 production was observed. Conclusions: To our knowledge this study shows for the first time that human detrusor smooth muscle cells cultivated under inflammatory conditions produce significant amounts of MCP-1. In addition to contractile function, HDSMCs have synthesis and secretory potential with the release of MCP-1. Thus, MCP-1 may contribute to the local inflammatory process by producing proinflammatory mediators. The release of cytokines and chemokines by human detrusor muscle even in small amounts may have important functional consequences.