BACKGROUND:Sulfasalazine has been used as anti-inflammatory and immunomodulatory drug in the treatment of Inflammatory bowel disease and rheumatoid arthritis,of which effect may be mediated through NFkappaB signaling interference by inhibition of IKappaB kinase.Sulfasalazine has been known to downregulate the expression of interleukin 8 in macrophage and monocyte chemotactic protein(MCP)-1 in endothelial cell which are important cytokines in neointimal hyperplasia.In recent years,IKappaB Kinase,the target of sulfasalazine,has been shown to phosphorylate and inhibit FOXO3a , a transcription factor which has been known to inhibit proliferation and induce apoptosis of vascular smooth muscle cell(VSMC) in neointimal hyperplasia. Here,we examined the effects of sulfasalazine on neointimal formation after balloon injury and its mechanism of action. METHODS :In vitro experiments were performed to evaluate the effects of sulfasalazine on the expression ofIL-8 in macrophages and MCP-1 in endothelial cells. Also the effects of sulfasalazine on FOXO3a activation and the viability of rat VSMCs was evaluated. In vivo experiments examined the effects of sulfasalazine on neointimal growth after denudation injury to rat carotid arteries. Results :In vitro,sulfasalazine suppressed the expression of IL-8 in macrophages and MCP-1 in endothelial cells.Sulfasalzine activated FOXO3a in cultured VSMCs,leading to a reduction in viable cell number and cell cycle arrest which was mediated by inhibition of IKappaB Kinase.In vivo, sulfasalazine reduced VSMC proliferation and increased Foxo activation and VSMC apoptosis at 3 days after injury.At 2 weeks after injury, sulfasalzine reduced intima-to-media ratio and the MCP-1 and IL-8 level in serum measured by ELISA was also significantly reduced by sulfasalazine.CONCLUSIONS:Sulfasalazine is a potential inhibitor of neointimal formation by inhibition of NFkappaB signaling.These findings suggest a potential use for sulfasalazine in the prevention of restenosis after angioplasty.