Increased retinoid signaling in vascular smooth muscle cells by proinflammatory cytokines

Retinoids have been shown to modulate inflammation and the immune response in many cell types including macrophages, endothelial cells, and vascular s mooth muscle cells. However, present knowledge of whether inflammatory medi ators modulate vitamin A status in these cells is limited. To identify the role of inflammation on retinoid metabolism in vascular smooth muscle cells , the cells were exposed to a combination of proinflammatory cytokines: int erleukin-1 beta, interferon-gamma, and lipopolysaccharides. Without stimula tion with proinflammatory cytokines, vascular smooth muscle cells expressed retinoldehydrogenases-2 and 5 mRNA detected by RT-PCR. Stimulation with th e combination of cytokines induced a substantial increase of retinol dehydr ogenase-5 mRNA. This was associated with increased production of ligands fo r retinoic acid receptors, when assayed in a retinoic acid receptor-depende nt luciferase reporter system. Our results demonstrate that inflammatory me diators activate the retinoid metabolic pathway in vascular smooth muscle c ells, which potentially may modulate the inflammatory response in the vascu lar wall. (C) 2001 Academic Press.