Garcia-Verdugo, Ignacio %A BenMohamed, Fatima %A Tattermusch, Sonja %A Leduc, Dominique %A Charpigny, Gilles %A Chignard, Michel %A Ollero, Mario %A Touqui,Lhousseine %T 12r -脂氧合酶在呼吸上皮细胞MUC5AC表达中的作用它们介导慢性肺部炎症性疾病的炎症和粘液分泌。在这些疾病患者的气道中,形成凝胶的粘蛋白MUC5AC过表达。MUC5AC的表达由细胞外信号调节激酶(ERK)/Sp1依赖机制介导。我们的目的是研究二十烷类化合物及其信号通路在MUC5AC表达中的作用。12-LOX的抑制剂,而COX、5-LOX或15-LOX的抑制剂,可降低NCI-H292支气管上皮细胞系中肉豆豆酸乙酸酯(PMA)诱导的MUC5AC表达。这些抑制剂也消除了由细胞单层产生的整个黏液。12-LOX有两种形式(R和S)存在于哺乳动物中。利用sirna,我们发现12R-LOX而不是12S-LOX参与了PMA、脂多糖或转化生长因子-α诱导的MUC5AC表达。 12R-LOX also participates in MUC2 and MUC5B expression, although to a lesser extent than for MUC5AC. Contrarily, 12R-LOX silencing does not modify interleukin-8 production. 12-LOX inhibitors reduce ERK activation and Sp1 translocation induced by PMA. Moreover, the 12R-LOX product 12(R)-hydroxyeicosatetraenoic acid, induces MUC5AC expression, ERK activation and Sp1 translocation. 12R-LOX is involved in MUC5AC expression. This occurs via ERK- and Sp1-signalling pathways. %U //www.qdcxjkg.com/content/erj/40/3/714.full.pdf