Functional and biochemical characterization of epithelial bactericidal/permeability-increasing protein
Functional and biochemical characterization of epithelial bactericidal/permeability-increasing protein
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DOI：
10.1152/ajpgi.00347.2005
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发表时间：
2006-03-01
影响因子：
4.5
通讯作者：
Colgan, SP
中科院分区：
文献类型：
--
作者：
Canny, G;Cario, E;Colgan, SP
上皮性杀菌/通透性增加蛋白的功能和生化特性。Am J Physiol胃肠病肝生理学290：G557-G567,2006。2005年11月10日首次出版；doi：10.1152/ajpgi.00347.2005。-许多粘膜器官的上皮细胞已经适应了与微生物和微生物产品共存。总的来说，大多数研究表明，上皮细胞受益于与管腔表面存在的共生微生物的相互作用。然而，在这种微环境中发现的潜在有害分子也有能力引发局部炎症反应，甚至引发全身疾病。我们最近证实，上皮细胞表达抗感染分子杀菌/通透性增加蛋白(BPI)。在这里，我们将这些发现扩展到研究肠上皮细胞(IEC)BPI表达和功能的分子机制。初步实验表明，不同的IEC株之间BPI的mRNA和蛋白表达存在差异。对BPI启动子在IECS中表达的研究发现了BPI启动子的调控区，并揭示了CCAAT/增强子结合蛋白，特别是Sp1/SP3在BPI的基础调控中的重要作用。为了评估该蛋白的功能意义，我们建立了稳定转染全长BPI的IEC系。我们证明，尽管上皮细胞表达的BPI蛋白明显少于中性粒细胞，但上皮细胞BPI在细菌杀灭和减弱细菌引发的促炎信号方面有显著贡献。在体外对小鼠组织的进一步研究表明，BPI沿着隐窝-绒毛轴扩散表达，上皮BPI水平沿着肠道的长度下降。综上所述，这些数据证实了BPI在肠道上皮细胞中的转录调控，并为BPI作为肠道表面抗感染分子的相关性提供了洞察。
Functional and biochemical characterization of epithelial bactericidal/permeability- increasing protein. Am J Physiol Gastrointest Liver Physiol 290: G557-G567, 2006. First published November 10, 2005; doi: 10.1152/ajpgi.00347.2005.-Epithelial cells of many mucosal organs have adapted to coexist with microbes and microbial products. In general, most studies suggest that epithelial cells benefit from interactions with commensal microorganisms present at the lumenal surface. However, potentially injurious molecules found in this microenvironment also have the capacity to elicit local inflammatory responses and even systemic disease. We have recently demonstrated that epithelia cells express the anti-infective molecule bactericidal/permeability-increasing protein (BPI). Here, we extend these findings to examine molecular mechanisms of intestinal epithelial cell (IEC) BPI expression and function. Initial experiments revealed a variance of BPI mRNA and protein expression among various IEC lines. Studies of BPI promoter expression in IECs identified regulatory regions of the BPI promoter and revealed a prominent role for CCAAT/enhancer binding protein and especially Sp1/Sp3 in the basal regulation of BPI. To assess the functional significance of this protein, we generated an IEC line stably transfected with full-length BPI. We demonstrated that, whereas epithelia express markedly less BPI protein than neutrophils, epithelial BPI contributes significantly to bacterial killing and attenuating bacterial-elicted proinflammatory signals. Additional studies in murine tissue ex vivo revealed that BPI is diffusely expressed along the crypt-villous axis and that epithelial BPI levels decrease along the length of the intestine. Taken together, these data confirm the transcriptional regulation of BPI in intestinal epithelia and provide insight into the relevance of BPI as an anti-infective molecule at intestinal surfaces.