TNF -induced GM-CSF release from human airway smooth muscle cells depends on activation of an ET-1 autoregulatory positive feedback mechanism

Abstract

TNFalpha activates an ET(A)R- and p38(MAPK)-dependent ET-1 autoregulatory positive feedback loop to maintain GM-CSF release from HASMCs. Since bosentan impairs ET-1 autoregulation and TNFalpha-induced ET-1 release, as well as TNFalpha- and ET-1-induced GM-CSF release, the present data suggest therapeutic utility for bosentan in treating particularly the early stages of chronic inflammatory airway diseases.