首页> 外文期刊>American Journal of Physiology >Lipopolysaccharide induces expression of fibronectin alpha 5 beta 1-integrin receptors in human monocytic cells in a protein kinase C-dependent fashion.
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Lipopolysaccharide induces expression of fibronectin alpha 5 beta 1-integrin receptors in human monocytic cells in a protein kinase C-dependent fashion.

机译:脂多糖以蛋白激酶C依赖性方式诱导人单核细胞中纤连蛋白α5β1-整联蛋白受体的表达。

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摘要

LPS is an outer-membrane glycolipid component of gram-negative bacteria known for its fervent ability to activate monocytic cells and for its potent proinflammatory capabilities. In addition, LPS triggers the release of cytokines and chemokines as well as cell-cell adhesion molecules. We postulate that LPS may also affect the expression of matrix-binding integrin receptors, thereby modulating cell-adhesive functions in monocytic cells. To test this hypothesis, we investigated the effects of LPS on the expression of the integrin alpha(5)beta(1), a fibronectin receptor, in a human monocytic cell line (U937) as well as in isolated human peripheral blood mononuclear cells (PBMCs). We found that LPS increased the expression of alpha(5)beta(1) receptors and enhanced the adherence of U937 cells and PBMCs to fibronectin-coated surfaces; this was blocked by anti-alpha(5)beta(1) antibodies. LPS increased alpha(5)-subunit mRNA accumulation in a dose- and time-dependent manner. The induction by LPS occurred, at least in part, at the level of gene transcription as indicated by experiments using alpha(5) intact and deletion promoter constructs. LPS-induced alpha(5) gene transcription was associated with rapid induction of conventional PKC-alpha protein and activity, was blocked by PKC inhibitors, and was mimicked by lipid A. Finally, we found that an anti-CD14 antibody was able to inhibit the LPS response. Overall, the data suggest that LPS stimulates alpha(5) gene transcription via CD14 and PKC-dependent signals to enhance the expression of functional alpha(5)beta(1) receptors in monocytic cells. This process may help stimulate monocytic cell activation and facilitate their migration into fibronectin-containing tissues during infection.
机译:LPS是革兰氏阴性细菌的外膜糖脂成分,以其强大的激活单核细胞能力和强大的促炎能力而著称。另外,LPS触发细胞因子和趋化因子以及细胞粘附分子的释放。我们推测LPS也可能影响基质结合整联蛋白受体的表达,从而调节单核细胞中的细胞黏附功能。为了验证这一假设,我们研究了LPS对人单核细胞系(U937)以及分离的人外周血单核细胞中纤连蛋白受体整联蛋白alpha(5)beta(1)表达的影响( PBMC)。我们发现LPS增加了alpha(5)beta(1)受体的表达,并增强了U937细胞和PBMC对纤连蛋白包被表面的粘附性;这被抗alpha(5)beta(1)抗体阻止。 LPS以剂量和时间依赖性方式增加了alpha(5)-亚基mRNA的积累。 LPS的诱导至少部分在基因转录水平上发生,如使用完整的α(5)和缺失启动子构建体的实验所表明的。 LPS诱导的alpha(5)基因转录与常规PKC-alpha蛋白和活性的快速诱导相关,被PKC抑制剂阻断,并被脂质A模仿。最后,我们发现抗CD14抗体能够抑制LPS响应。总体而言,数据表明LPS通过CD14和PKC依赖性信号刺激alpha(5)基因转录,以增强单核细胞中功能性alpha(5)beta(1)受体的表达。这个过程可能有助于刺激单核细胞活化,并促进它们在感染过程中迁移到含纤连蛋白的组织中。

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