G protein-coupled receptors (GPCRs) comprise the largest family of integral membrane proteins of humans, and these receptors are among the most pursued targets for therapies. Endothelin-1 type A receptor  (ETAR) has a pivotal role in promoting migration of immune and non-immune cells. A relation between high titers of anti-ETAR, increased levels of natural ET-1 and alteration in ETAR expression has been described in different autoimmune diseases. However, the regulation of ETAR expression on immune cells such as neutrophils, which play an important role in various autoimmune diseases remain poorly investigated.

It is well known that abnormal pro- and anti-inflammatory cytokines produced by T helper (Th)1 and Th2 cells (e.g. IFN-γ and IL-4, etc.) as well as soluble factors such as soluble CD40L (sCD40L) have multiple functions  in the pathogenesis of autoimmune diseases. Despite of that, their effects on ETAR expression have not been investigated.

We tested the effect of ambrisentan on cell migration. After one hour in the presence of ETAR antagonist ambrisentan, neutrophils lost their capacity to spontaneously migrate and to migrate in response to fMLP. Considering the essential and non-redundant role that ETAR plays in the regulation of cell migration. Therefore, my project aims to identify modulators of ETAR expression and signaling in neutrophils.