Irap inhibitors for use in the treatment of inflammatory diseases

Abstract

Upon activation, mast cells rapidly release preformed inflammatory mediators from large cytoplasmic granules via regulated exocytosis. This acute degranulation is followed by a late activation phase involving synthesis and secretion of cytokines, growth factors and other inflammatory molecules via the constitutive pathway that remains ill-defined. Here the inventors describe a role for an insulin-responsive vesicle-like endosomal compartment, marked by insulin-regulated aminopeptidase (IRAP), in the secretion of TNF-α and IL-6 in mast cells and macrophages. IRAP-deficient mice are protected from TNF-dependent kidney injury and inflammatory arthritis. In the absence of IRAP, TNF fails to be efficiently exported from the Golgi. Chemical targeting of IRAP+ endosomes reduced pro-inflammatory cytokine secretion thereby highlighting this compartment as a promising target for the therapeutic control of inflammation. Thus the present invention relates to the use of IRAP inhibitors for the treatment of inflammatory diseases

Dependencies are inferred from the claim text.