Lipopolysaccharide-Binding Protein Downregulates Fractalkine through Activation of p38 MAPK and NF-κB.
Lipopolysaccharide-Binding Protein Downregulates Fractalkine through Activation of p38 MAPK and NF-κB.
复制标题
脂多糖结合蛋白通过激活 p38 MAPK 和 NF-kappa B 下调 Fractalkine
DOI：
10.1155/2017/9734837
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发表时间：
2017
影响因子：
4.6
通讯作者：
Pinhu L
中科院分区：
文献类型：
--
作者：
Huang X;Zeng Y;Jiang Y;Qin Y;Luo W;Xiang S;Sooranna SR;Pinhu L
已知LBP和Fractalkine参与ARDS的发病机制。本研究通过建立大鼠急性呼吸窘迫综合征（ARDS）模型，探讨LPS诱导的A549细胞和大鼠肺组织中LBP和Fractalkine的关系。 用LBP或LBP shRNA质粒DNA转染A549细胞，或在LPS处理后用SB 203580或SC-514预处理。使用LPS与或不与LBPK 95 A、SB 203580或SC-514治疗建立ARDS大鼠模型。采用RT-PCR、Western blotting、ELISA、免疫荧光、免疫共沉淀、免疫组化等方法检测Fractalkine、LBP的表达及p38 MAPK、p65 NF-κB活性。 LPS使LBP升高，Fractalkine降低。LBP过表达进一步降低了LPS诱导的A549细胞中fractalkine和p38 MAPK以及p65 NF-κB活化的下调; LBP基因沉默、SB 203580和SC-514抑制了LPS诱导的A549细胞中fractalkine和p38 MAPK以及p65 NF-κB活化的下调。肺组织中LBP和Fractalkine在LPS注射后分别升高和降低。LBPK 95 A、SB 203580和SC-514通过降低磷酸化p38 MAPK和p65 NF-κB，减轻LPS诱导的大鼠肺损伤，并抑制LPS诱导的fractalkine下调。 结果表明LBP通过激活p38 MAPK和NF-κB下调LPS诱导的A549细胞和ARDS大鼠模型中Fractalkine的表达。
LBP and fractalkine are known to be involved in the pathogenesis of ARDS. This study investigated the relationship between LBP and fractalkine in LPS-induced A549 cells and rat lung tissue in an ARDS rat model. A549 cells were transfected with LBP or LBP shRNA plasmid DNA or pretreated with SB203580 or SC-514 following LPS treatment. An ARDS rat model was established using LPS with or without LBPK95A, SB203580, or SC-514 treatment. RT-PCR, western blotting, ELISA, immunofluorescence, coimmunoprecipitation, and immunohistochemical staining were used to study the expression of fractalkine and LBP and p38 MAPK and p65 NF-κB activities. LPS increased LBP and reduced fractalkine. LBP overexpression further decreased LPS-induced downregulation of fractalkine and p38 MAPK and p65 NF-κB activation; LBP gene silencing, SB203580, and SC-514 suppressed LPS-induced downregulation of fractalkine and p38 MAPK and p65 NF-κB activation in A549 cells. LBP and fractalkine in lung tissue were increased and decreased, respectively, following LPS injection. LBPK95A, SB203580, and SC-514 ameliorated LPS-induced rat lung injury and suppressed LPS-induced downregulation of fractalkine by decreasing phospho-p38 MAPK and p65 NF-κB. The results indicate that LBP downregulates fractalkine expression in LPS-induced A549 cells and in an ARDS rat model through activation of p38 MAPK and NF-κB.