Endothelin Receptors Expressed by Immune Cells Are Involved in Modulation of Inflammation and in Fibrosis: Relevance to the Pathogenesis of Systemic Sclerosis

摘要: Endothelin-1 (ET-1) plays a pivotal role in vasoconstriction, fibrosis, and inflammation, the key features of systemic sclerosis (SSc). ET-1 receptors (ETA ET(B)) are expressed on endothelial cells, smooth muscle fibroblasts, but their presence immune cells has not been deeply investigated so far. Endothelin antagonists such as bosentan have beneficial effects vasoconstriction less is known about potential anti-inflammatory effects. We studied expression (T B lymphocytes, monocytes, neutrophils) link between inflammation patients with SSc. show here that exerts proinflammatory effect CD4+ T since it induces an increased IFN-γ production; preincubation both reduces production. Moreover, following stimulation, neutrophils produce mediators, thus amplifying activated cells. Our data indicate system involved pathogenesis fibrosis typical SSc, through activation lymphocytes consequent release profibrotic cytokines. These findings suggest dual antagonist therapy, besides its vasculopathy, profound impact favouring antiinflammatory antifibrogenic