Host defense against pathogens relies on neutrophil activation. Inadequate neutrophil activation is often associated with chronic inflammatory diseases. Neutrophils also constitute a significant portion of infiltrating cells in chronic inflammatory diseases, for example, @entity1569 and @entity15 . Fumarates improve the latter diseases, which so far has been attributed to the effects on lymphocytes and dendritic cells. Here, we focused on the effects of @entity15626 ( @entity9104 ) on neutrophils. In  vitro, @entity9104 inhibited neutrophil activation, including changes in surface marker expression, reactive @entity26 species production, formation of neutrophil extracellular traps, and migration. Phagocytic ability and autoantibody-induced, neutrophil-dependent tissue injury ex  vivo was also impaired by @entity9104 . Regarding the mode of action, @entity9104 modulates-in a stimulus-dependent manner-neutrophil activation using the @entity7425 3-kinase/Akt-p38 mitogen-activated protein kinase and extracellular signal-regulated kinase 1/2 pathways. For in  vivo validation, @entity19 models of @entity27889 , an organ-specific @entity792 caused by autoantibodies to type VII collagen, were employed. In the presence of @entity9104 , blistering induced by injection of anti-type VII collagen antibodies into @entity19 was significantly impaired. @entity9104 treatment of @entity19 with clinically already-manifested @entity27889 led to disease improvement. Collectively, we demonstrate a profound inhibitory activity of @entity9104 on neutrophil functions. These findings encourage wider use of @entity9104 in @entity1 with neutrophil-mediated diseases.

XXXX Impairs Neutrophil Functions.

@entity1 :: ('9606', 'Species') :: ['patients'] @entity1569 :: ('MESH:D011565', 'Disease') :: ['psoriasis'] @entity27889 :: ('MESH:D016107', 'Disease') :: ['epidermolysis bullosa acquisita'] @entity7425 :: ('CHEBI:18179', 'Chemical') :: ['phosphoinositide'] @entity19 :: ('10090', 'Species') :: ['mice', 'mouse'] @entity9104 :: ('CHEBI:17741', 'Chemical') :: ['DMF'] @entity26 :: ('MESH:D010100', 'Chemical') :: ['oxygen'] @entity15626 :: ('MESH:C056020', 'Chemical') :: ['dimethylfumarate'] @entity792 :: ('MESH:D001327', 'Disease') :: ['autoimmune disease'] @entity15 :: ('MESH:D009103', 'Disease') :: ['multiple sclerosis']
@entity15626 :: (MESH:C056020,Chemical) :: ['Dimethylfumarate']
