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-1 beta (IL-1 beta), tumor necrosis factor (TNF-alpha), lipopolysaccharide, histamine, leukotriene D4 and prostaglandin E2. 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-1 beta or TNF-alpha (1 pg/ml to 100 ng/ml) the level of MCP-1 increased in a dose dependent manner. IL-1 beta was more potent at inducing MCP-1 release in 8 of 10 experiments. Lipopolysaccharide (10 microg/ml), histamine (100 microM), leukotriene D4 (50 nM), prostaglandin E2 (1 microM) and KCl (30 to 100 mM) failed to induce MCP-1 production. When IL-1 beta (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.
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-1 beta (IL-1 beta), tumor necrosis factor (TNF-alpha), lipopolysaccharide, histamine, leukotriene D4 and prostaglandin E2. 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-1 beta or TNF-alpha (1 pg/ml to 100 ng/ml) the level of MCP-1 increased in a dose dependent manner. IL-1 beta was more potent at inducing MCP-1 release in 8 of 10 experiments. Lipopolysaccharide (10 microg/ml), histamine (100 microM), leukotriene D4 (50 nM), prostaglandin E2 (1 microM) and KCl (30 to 100 mM) failed to induce MCP-1 production. When IL-1 beta (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.
Authors: Francis M Hughes; Nivardo P Vivar; James G Kennis; Jeffery D Pratt-Thomas; Danielle W Lowe; Brooke E Shaner; Paul J Nietert; Laura S Spruill; J Todd Purves Journal: Am J Physiol Renal Physiol Date: 2013-11-27
Authors: Hitoshi Yokoyama; Tomohiko Oguchi; William F Goins; James R Goss; Osamu Nishizawa; William C de Groat; Darren Wolfe; David M Krisky; Joseph C Glorioso; Naoki Yoshimura Journal: Hum Gene Ther Date: 2013-02-14 Impact factor: 5.695