GEC 衍生的 SFRP5 抑制 Wnt5a 诱导的巨噬细胞趋化和激活。
GEC-derived SFRP5 inhibits Wnt5a-induced macrophage chemotaxis and activation.
机构信息
Department of Pathophysiology, College of Basic Medical Science, China Medical University, Shenyang, China.
Department of General Surgery, Shengjing Hospital, China Medical University, Shenyang, China.
出版信息
PLoS One. 2014 Jan 8;9(1):e85058. doi: 10.1371/journal.pone.0085058. eCollection 2014.
Aberrant macrophage infiltration and activation has been implicated in gastric inflammation and carcinogenesis. Overexpression of Wnt5a and downregulation of SFRP5, a Wnt5a antagonist, were both observed in gastric cancers recently. This study attempted to explore whether Wnt5a/SFRP5 axis was involved in macrophage chemotaxis and activation. It was found that both Wnt5a transfection and recombinant Wnt5a (rWnt5a) treatment upregulated CCL2 expression in macrophages, involving JNK and NFκB signals. Conditioned medium from Wnt5a-treated macrophages promoted macrophage chemotaxis mainly dependent on CCL2. SFRP5 from gastric epithelial cells (GECs) inhibited Wnt5a-induced CCL2 expression and macrophage chemotaxis. In addition, Wnt5a treatment stimulated macrophages to produce inflammatory cytokines and COX-2/PGE2, which was also suppressed by SFRP5 from GECs. These results demonstrate that Wnt5a induces macrophage chemotaxis and activation, which can be blocked by GEC-derived SFRP5, suggesting that Wnt5a overproduction and SFRP5 deficiency in gastric mucosa may together play an important role in gastric inflammation and carcinogenesis.
异常的巨噬细胞浸润和激活与胃炎症和癌变有关。最近在胃癌中观察到 Wnt5a 的过表达和 Wnt5a 拮抗剂 SFRP5 的下调。本研究试图探讨 Wnt5a/SFRP5 轴是否参与巨噬细胞趋化和激活。结果发现，Wnt5a 转染和重组 Wnt5a(rWnt5a)处理均上调了巨噬细胞中 CCL2 的表达，涉及 JNK 和 NFκB 信号。Wnt5a 处理的巨噬细胞条件培养基主要依赖于 CCL2 促进巨噬细胞趋化。胃上皮细胞 (GEC) 中的 SFRP5 抑制 Wnt5a 诱导的 CCL2 表达和巨噬细胞趋化。此外，Wnt5a 处理刺激巨噬细胞产生炎症细胞因子和 COX-2/PGE2，这也被 GEC 来源的 SFRP5 抑制。这些结果表明，Wnt5a 诱导巨噬细胞趋化和激活，这可以被胃黏膜中 GEC 衍生的 SFRP5 阻断，提示胃黏膜中 Wnt5a 过度产生和 SFRP5 缺乏可能共同在胃炎症和癌变中发挥重要作用。
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