Surfactant blocks lipopolysaccharide signaling by inhibiting both mitogen-activated protein and IkappaB kinases in human alveolar macrophages.
Surfactant blocks lipopolysaccharide signaling by inhibiting both mitogen-activated protein and IkappaB kinases in human alveolar macrophages.
复制标题
表面活性剂通过抑制人肺泡巨噬细胞中的丝裂原激活蛋白和 IkappaB 激酶来阻断脂多糖信号传导。
DOI：
10.1165/rcmb.2003-0263oc
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发表时间：
2004
影响因子：
6.4
通讯作者：
Thomassen,MaryJane
中科院分区：
文献类型：
--
作者：
Raychaudhuri,Baisakhi;Abraham,Susamma;Bonfield,TraceyL;Malur,Anagha;Deb,Amitabha;DiDonato,JosephA;Kavuru,ManiS;Thomassen,MaryJane
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 lung diseases such as acute respiratory distress syndrome and pneumonia, among others. Our previous studies demonstrated that the clinically used, natural surfactant product Survanta inhibited proinflammatory cytokine secretion from LPS-stimulated human alveolar macrophages. Here we investigated the effect of Survanta on mitogen-activated protein (MAP) and IκB kinases. Survanta blocked LPS-induced activation of nuclear factor-κB, a key regulatory transcription factor involved in cytokine production, by preventing phosphorylation of IκBα, and its subsequent degradation. IκB is phosphorylated by specific kinases (IKK) before degradation. Survanta inhibited activity of both α and β subunits of IKK, thereby delaying the phosphorylation of IκB. Interestingly, IKK-α is predominant in alveolar macrophages, whereas IKK-β predominates in monocytes. Survanta also inhibited extracellular signal–regulated kinase and p38 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.
