Zhou Z, Jing Y, Ran Y, Zhao J, Zhou L, Wang B M
Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin 300052, China.
Zhonghua Nei Ke Za Zhi. 2018 Apr 1;57(4):279-284. doi: 10.3760/cma.j.issn.0578-1426.2018.04.010.
To evaluate the changes of macrophages and expression of Rac1 in the inflammatory site of Crohn's disease, and to investigate the effects of 6-thioguanine (6-TG) and peptidoglycan on apoptosis of human peripheral blood monocyte-macrophage by regulating Rac1 signaling pathway. Ten patients with Crohn's disease and eight healthy controls diagnosed were enrolled at Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital from January 2013 to January 2014. The number of macrophages, apoptosis and expression of Rac1 in the inflammation sites and non-inflammation sites of intestinal mucosa were detected in both patients and controls. Peripheral blood mononuclear cells (PBMCs) were sorted by CD immunomagnetic beads. The apoptosis of monocytes, expression of Rac1 and related apoptosis signaling molecules were detected in patients treated with peptidoglycan, 6-TG and Rac1 inhibitor NSC23766 and another 15 healthy donors. The number of macrophages and apoptotic cells significantly increased in the inflammatory group of Crohn's disease patients compared with the non-inflammatory group. The expression of PAK1, downstream molecular of Rac1 signaling pathway of macrophages was also significantly higher in the inflammatory group of Crohn's disease patients than that in healthy controls and non-inflammatory group. Compared with control group, anti-apoptotic signals (NF-κB, Bcl-xL and STAT-3) in PBMCs increased in the peptidoglycan group, while slightly decreased in 6-TG group. 6-TG and NSC23766 significantly promoted peptidoglycan-related anti-apoptosis [peptidoglycan group (8.6±3.7)%, peptidoglycan+ 6-TG group (42.0±2.7)%, peptidoglycan+ NSC23766 group (58.5±6.9)%, 0.05]. Peptidoglycan plays a role in the pathogenesis of Crohn's disease by recruiting macrophages. However, 6-TG inhibits peptidoglycan-induced activation of Rac1 signaling pathway leading to macrophage apoptosis.
评估克罗恩病炎症部位巨噬细胞变化及Rac1表达，探讨6-硫鸟嘌呤（6-TG）和肽聚糖通过调节Rac1信号通路对人外周血单核细胞-巨噬细胞凋亡的影响。2013年1月至2014年1月，天津医科大学总医院消化内科和肝病科纳入10例克罗恩病患者及8例健康对照者。检测患者和对照者肠黏膜炎症部位和非炎症部位巨噬细胞数量、凋亡情况及Rac1表达。采用CD免疫磁珠分选外周血单个核细胞（PBMC）。检测肽聚糖、6-TG和Rac1抑制剂NSC23766处理的患者及另外15例健康供者单核细胞凋亡、Rac1表达及相关凋亡信号分子情况。与非炎症组相比，克罗恩病患者炎症组巨噬细胞和凋亡细胞数量显著增加。克罗恩病患者炎症组巨噬细胞Rac1信号通路下游分子PAK1表达也显著高于健康对照者和非炎症组。与对照组相比，肽聚糖组PBMC中抗凋亡信号（NF-κB、Bcl-xL和STAT-3）增加，而6-TG组略有下降。6-TG和NSC23766显著促进肽聚糖相关的抗凋亡作用[肽聚糖组（8.6±3.7）%，肽聚糖+6-TG组（42.0±2.7）%，肽聚糖+NSC23766组（58.5±6.9）%，P<0.05]。肽聚糖通过募集巨噬细胞在克罗恩病发病机制中起作用。然而，6-TG抑制肽聚糖诱导的Rac1信号通路激活导致巨噬细胞凋亡。
