Endothelin-1 could be one of the targets of psoriasis therapy

Abstract

Sir, All current treatments for psoriasis have limitations, particularly for severely affected patients. The pathogenesis of this inflammatory skin disorder that may affect about 1–3% of the world population1 is still under debate. One of the principal clinical aspects of psoriasis is the hyperproliferation of keratinocytes in some skin areas via the action of inflammatory mediators. Controlling this upregulated growth would be a very attractive therapy even if the causative agent(s) of the disease cannot be blocked. The active vitamin D3 analogues tacalcitol, calcipotriol and maxacalcitol are examples of an effective treatment which addresses keratinocyte hyperproliferation2 without affecting the underlying cause of the disease. Keratinocytes can produce cytokines and growth factors, and some of these can stimulate cell proliferation through an autocrine loop. Several years ago it was reported by our group that endothelin (ET)‐1 is produced in keratinocytes and acts through the ETA receptor as an autocrine growth factor for these cells.3 ETs are a family of three vasoactive peptides, termed ET‐1, ET‐2 and ET‐3, which induce their biological actions through at least two major receptor subtypes that belong to the family of G‐protein coupled receptors: a selective ETA receptor, which binds ET‐1 and ET‐2 with high affinity and ET‐3 with low affinity, and a nonselective ETB receptor which binds all ET isopeptides with equal affinity. It has recently been reported that compounds t…