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首页> 外文期刊>Biochemical Pharmacology >WNK4-SPAK modulates lipopolysaccharide-induced macrophage activation
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WNK4-SPAK modulates lipopolysaccharide-induced macrophage activation

机译:Wnk4-静止调节脂多糖诱导的巨噬细胞活化

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Dysregulation of alveolar macrophage activation has been recognized as the major mechanism in the pathogenesis of acute lung injury. The aim of the present study was to investigate the role of NKCC1 regulating mechanism in modulating macrophage activation. Knockout (SPAK(-/-) and WNK4(-/-)) and knockin (WNK4(D561A/+)) mice were used in this study. LPS induced expression of p-NKCC1 and activation of NF kappa B in the primary culture of alveolar macrophages. WNK4 or SPAK knockout suppressed p-NKCC1 expression and inflammation cascade activation, whereas WNK4 knockin enhanced these responses. Intrapulmonary administration of LPS induced in vivo expression and phosphorylation of NKCC1 in alveolar inflammation cells and caused a shift in the cell population from macrophage to neutrophil predominance. WNK4 or SPAK knockout attenuated the LPS-induced alveolar cell-population shifting, macrophage NKCC1 phosphorylation, and acute lung injury, whereas WNK4 knockin augmented the inflammatory response. In summary, our results demonstrated the presence of NKCC1 in alveolar macrophage, which is inducible by lipopolysaccharide. Our results also showed showed that the WNK4-SPAK-NKCC1 cascade plays an important role in modulating macrophage activation to regulate LPS-induced lung inflammation and lung injury.
机译:肺泡巨噬细胞活化的失调被认为是急性肺损伤发病机制中的主要机制。本研究的目的是探讨NKCC1调节机制在调节巨噬细胞激活中的作用。在本研究中使用敲除(Spak( - / - )和WNK4( - / - ))和Knockin(WNK4(D561A / +)小鼠。 LPS在肺泡巨噬细胞初级培养中诱导P-NKCC1的表达和NFκB的激活。 Wnk4或spak敲除抑制了p-nkcc1表达和炎症级联激活,而Wnk4敲蛋白增强了这些反应。在肺泡炎症细胞中体内表达和NKCC1的磷酸化诱导的LPS的肺内施用,并导致来自巨噬细胞的细胞群转移到中性粒细胞优势。 Wnk4或Spak敲除减弱LPS诱导的肺泡细胞群移位,巨噬细胞NKCC1磷酸化和急性肺损伤,而WNK4敲蛋白增强了炎症反应。总之,我们的结果证明存在NKCC1在肺泡巨噬细胞中,这是由脂多糖诱导的。我们的研究结果表明,WNK4-SPAK-NKCC1级联在调节巨噬细胞激活以调节LPS诱导的肺炎和肺损伤方面发挥着重要作用。

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