The role and mechanism of KCa3.1 channels in human monocyte migration induced by palmitic acid
The role and mechanism of KCa3.1 channels in human monocyte migration induced by palmitic acid
复制标题
KCa3.1通道在棕榈酸诱导人单核细胞迁移中的作用及机制
DOI：
10.1016/j.yexcr.2018.05.020
复制
发表时间：
2018
期刊：
影响因子：
--
通讯作者：
Deng XL
中科院分区：
文献类型：
--
作者：
Ma XZ;Pang ZD;Wang JH;Song Z;Zhao LM;Du XJ;Deng XL
单核细胞迁移到患病组织有助于疾病的发病机制。中电导Ca ~（2+）激活的K ~+（KCa ~（3.1））通道在细胞迁移中起重要作用。然而，KCa 3.1通道在介导棕榈酸（PA）诱导的单核细胞迁移中的作用仍不清楚。本研究以体外培养的THP-1细胞和健康人外周血单个核细胞为研究对象，探讨KCa 3.1通道在PA诱导的THP-1细胞迁移中的作用及其信号转导机制。通过Western blotting、RNA干扰、细胞迁移实验和ELISA等方法，我们发现PA处理的单核细胞KCa 3.1通道和单核细胞趋化蛋白-1（MCP-1）的蛋白水平增加，而PA与抗TLR 2/4抗体或p38-MAPK、NF-κB特异性抑制剂共同孵育可逆转这种作用。此外，PA增加单核细胞迁移，这是废除了特定的KCa3.1通道阻滞剂，TRAM-34，或KCa3.1小干扰RNA（siRNA）。TRAM-34和KCa 3.1 siRNA也同样抑制PA诱导的MCP-1表达和分泌。以上结果首次证明PA通过TLR 2/4、p38-MAPK和NF-κB B途径上调KCa 3.1通道，促进MCP-1的表达，进而诱导单核细胞跨内皮迁移。
Monocyte migration into diseased tissues contributes to the pathogenesis of diseases. Intermediate-conductance Ca2+-activated K+(KCa3.1) channels play an important role in cell migration. However, the role of KCa3.1 channels in mediating monocyte migration induced by palmitic acid (PA) is still unclear. Using cultured THP-1 cells and peripheral blood mononuclear cells from healthy subjects, we investigated the role and signaling mechanisms of KCa3.1 channels in mediating the migration induced by PA. Using methods of Western blotting analysis, RNA interference, cell migration assay and ELISA, we found that PA-treated monocytes exhibited increment of the protein levels of KCa3.1 channel and monocyte chemoattractant protein-1 (MCP-1), and the effects were reversed by co-incubation of PA with anti-TLR2/4 antibodies or by specific inhibitors of p38-MAPK, or NF-κB. In addition, PA increased monocyte migration, which was abolished by a specific KCa3.1 channel blocker, TRAM-34, or KCa3.1 small interfering RNA (siRNA). The expression and secretion of MCP-1 induced by PA was also similarly prevented by TRAM-34 and KCa3.1 siRNA. These results demonstrate for the first time that PA upregulates KCa3.1 channels through TLR2/4, p38-MAPK and NF-κB pathway to promote the expression of MCP-1, and then induce the trans-endothelial migration of monocytes.