Surfactant plays an important role in lung homeostasis and is also involved in maintaining innate immunity within the lung. Lipopolysaccharide (LPS) from gram-negative bacteria is known to elicit acute proinflammatory responses in @entity358 such as @entity649 and @entity55 , among others. Our previous studies demonstrated that the clinically used, natural surfactant product Survanta inhibited proinflammatory cytokine secretion from LPS-stimulated @entity1 alveolar macrophages. Here we investigated the effect of Survanta on mitogen-activated protein (MAP) and IkappaB kinases. Survanta blocked LPS-induced activation of nuclear factor-kappaB, a key regulatory transcription factor involved in cytokine production, by preventing phosphorylation of @entity4284 , and its subsequent degradation. IkappaB is phosphorylated by specific kinases (IKK) before degradation. Survanta inhibited activity of both alpha and beta subunits of IKK, thereby delaying the phosphorylation of IkappaB. Interestingly, @entity18159 is predominant in alveolar macrophages, whereas @entity15955 predominates in monocytes. Survanta also inhibited extracellular signal-regulated kinase and @entity1435 MAP kinase activity induced by LPS. Data are the first to show that surfactant may regulate lung homeostasis in part by inhibiting proinflammatory cytokine production through reduction of IKK and MAP kinase activity.

Surfactant blocks lipopolysaccharide signaling by inhibiting both mitogen-activated protein and IkappaB kinases in XXXX alveolar macrophages.

@entity1 :: ('9606', 'Species') :: ['human'] @entity55 :: ('MESH:D011014', 'Disease') :: ['pneumonia'] @entity15955 :: ('3551', 'Gene') :: ['IKK-beta'] @entity649 :: ('MESH:D012128', 'Disease') :: ['acute respiratory distress syndrome'] @entity4284 :: ('4792', 'Gene') :: ['IkappaBalpha'] @entity358 :: ('MESH:D008171', 'Disease') :: ['lung diseases'] @entity18159 :: ('1147', 'Gene') :: ['IKK-alpha'] @entity1435 :: ('1432', 'Gene') :: ['p38']
@entity1 :: (9606,Species) :: ['human']
