CXCR4 knockdown prevents inflammatory cytokine expression in macrophages by suppressing activation of MAPK and NF-κB signaling pathways
CXCR4 knockdown prevents inflammatory cytokine expression in macrophages by suppressing activation of MAPK and NF-κB signaling pathways
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CXCR4 敲低通过抑制 MAPK 和 NF-κ B 信号通路的激活来防止巨噬细胞中炎症细胞因子的表达
DOI：
10.1186/s13578-019-0315-x
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发表时间：
2019-07-03
影响因子：
7.5
通讯作者：
Zhang, Min
中科院分区：
文献类型：
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作者：
Tian, Xue;Xie, Guogang;Zhang, Min
最近的证据表明，C-X-C趋化因子受体4型（CXCR4）在急性肺损伤（ALI）中起着至关重要的作用。巨噬细胞是ALI发病的关键因素。本研究旨在探讨CXCR4在脂多糖（LPS）刺激后巨噬细胞中的作用，并证实CXCR4敲低可通过抑制丝裂原活化蛋白激酶（MAPK）和核因子κ B （nf - κ B）信号通路激活来抑制炎症细胞因子。结果在本研究中，我们使用免疫荧光法发现急性肺损伤肺组织中CXCR4的表达明显升高。我们还通过RT-qPCR发现，从ALI的支气管肺泡灌洗液（BALF）中提取的巨噬细胞中CXCR4的表达明显上调。使用siRNA敲低CXCR4后，我们发现巨噬细胞中白细胞介素-6 （IL-6）和肿瘤坏死因子α (tnf - α)的表达明显下调。此外，通过western blotting检测，CXCR4敲除后，p38、Erk和p65的磷酸化水平显著降低。综上所述，本研究提示CXCR4敲低可能通过抑制MAPK和NF-kappa B信号通路的激活来抑制巨噬细胞炎症细胞因子的表达。因此，CXCR4敲低可能在治疗ALI中具有潜在的临床价值。
BackgroundRecent evidence has shown that C-X-C chemokine receptor type 4 (CXCR4) plays a crucial role in acute lung injury (ALI). Macrophages are key factors in the pathogenesis of ALI. The aim of this study was to investigate the role of CXCR4 in macrophages after lipopolysaccharide (LPS) stimulation and confirm that CXCR4 knockdown can inhibit inflammatory cytokines by suppressing mitogen-activated protein kinase (MAPK) and nuclear factor-kappa B (NF-kappa B) signaling pathway activation.ResultsIn this study, we found that CXCR4 expression in lung tissue of ALI was significantly increased using immunofluorescence. We also found that the expression of CXCR4 in macrophages sorted from bronchoalveolar lavage fluid (BALF) of ALI was obviously upregulated through RT-qPCR. After CXCR4 knockdown using siRNA, we found that the expression of interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-alpha) was obviously down regulated in macrophages. Additionally, the phosphorylation of p38, Erk, and p65 was significantly decreased after CXCR4 knockdown through western blotting.ConclusionsTaken together, the present study suggests that CXCR4 knockdown may inhibit inflammatory cytokine expression in macrophages by suppressing MAPK and NF-kappa B signaling pathway activation. Therefore, CXCR4 knockdown may have potential clinical value in treating ALI.