Inducible expression of an antibiotic peptide gene in lipopolysaccharide-challenged tracheal epithelial cells
Inducible expression of an antibiotic peptide gene in lipopolysaccharide-challenged tracheal epithelial cells
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DOI：
10.1073/pnas.93.10.5156
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发表时间：
1996-05-14
影响因子：
11.1
通讯作者：
Bevins, CL
中科院分区：
文献类型：
--
作者：
Diamond, G;Russell, JP;Bevins, CL
哺乳动物不断地在粘膜表面面对微生物。目前的模型表明，上皮细胞有助于在这些网站的防御，部分通过生产广谱抗生素肽。先前的研究已经表明，无脊椎动物可以发起宿主防御反应，其特征在于当它们受到微生物、细菌细胞壁/膜组分或创伤性损伤的攻击时，在上皮细胞中诱导多种抗生素蛋白和肽[Boman，H. G. & Hultmark，D.（1987）Annu. Rev. Microbiol. 41，103-126]。然而，在哺乳动物上皮细胞中控制类似防御分子表达的因素知之甚少。在这里，13倍的诱导内源性基因编码气管抗菌肽被发现表征宿主反应的气管上皮细胞（TEC）暴露于细菌脂多糖（LPS）。北方印迹数据表明，TEC表达CD 14，一种已知介导许多LPS应答的充分表征的LPS结合蛋白。在无血清条件下，CD 14单克隆抗体阻断了LPS诱导的气管抗菌肽。总之，这些数据支持上皮细胞来源的CD 14介导TEC中抗生素肽基因的LPS诱导，为上皮细胞积极参与宿主对细菌的局部防御反应提供了证据。此外，这些数据暗示了这种宿主反应在进化中的保守性，并表明在哺乳动物的粘膜表面普遍存在类似的宿主防御诱导途径。
Mammals continually confront microbes at mucosal surfaces. A current model suggests that epithelial cells contribute to defense at these sites, in part through the production of broad-spectrum antibiotic peptides. Previous studies have shown that invertebrates can mount a host defense response characterized by the induction in epithelial cells of a variety of antibiotic proteins and peptides when they are challenged with microorganisms, bacterial cell wall/membrane components, or traumatic injury [Boman, H.G. & Hultmark, D. (1987) Annu. Rev. Microbiol. 41, 103-126]. However, factors that govern the expression of similar defense molecules in mammalian epithelial cells are poorly understood. Here, a 13-fold induction of the endogenous gene encoding tracheal antimicrobial peptide was found to characterize a host response of tracheal epithelial cells (TECs) exposed to bacterial lipopolysaccharide (LPS). Northern blot data indicated that TECs express CD14, a well-characterized LPS-binding protein known to mediate many LPS responses. A monoclonal antibody to CD14 blocked the observed tracheal antimicrobial peptide induction by LPS under serum-free conditions. Together the data support that CD14 of epithelial cell origin mediates the LPS induction of an antibiotic peptide gene in TECs, providing evidence for the active participation of epithelial cells in the host's local defense response to bacteria. Furthermore, the data allude to a conservation of this host response in evolution and suggest that a similar inducible pathway of host defense is prevalent at mucosal surfaces of mammals.