Research Center of Integrative Medicine, School of Basic Medical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, 510006, Guangdong, PR China.
Clinical Medical of Acupuncture, Moxibustion and Rehabilitation, Guangzhou University of Chinese Medicine, Guangzhou, 510006, Guangdong, PR China.
Exp Cell Res. 2020 Aug 1;393(1):112037. doi: 10.1016/j.yexcr.2020.112037. Epub 2020 Apr 28.
Phagocytosis is a basic immune response to the invasion of pathogens. High mobility group protein B1 (HMGB1) is a DNA chaperone that is associated with phagocytosis. However, its influence on phagocytosis is debated. In the present study, HMGB1-mutant, HMGB1-overexpressing and HMGB1-silenced RAW264.7 cells were constructed. In addition, HMGB1 conditional knockout mice were constructed to determine the influence of HMGB1 on phagocytosis. Lipopolysaccharide (LPS) was used to stimulate the translocation of HMGB1 from the nucleus to the cytoplasm. Zymosan particles were used to test the phagocytic function of the macrophages. Our results showed that the accumulation of HMGB1 in the nucleus enhances the phagocytic function of the macrophages. By interacting with P53, nuclear HMGB1 may remain in the nucleus and decrease the negative influence of P53 on the phosphorylation of focal adhesion kinase (FAK). The increase in phosphorylated FAK promotes the formation of pseudopods and enhances the phagocytic ability of macrophages.
吞噬作用是机体针对病原体入侵的一种基本免疫反应。高迁移率族蛋白 B1(HMGB1)是一种与吞噬作用相关的 DNA 伴侣蛋白。然而,其对吞噬作用的影响存在争议。在本研究中,构建了 HMGB1 突变体、HMGB1 过表达和 HMGB1 沉默 RAW264.7 细胞,并构建了 HMGB1 条件敲除小鼠,以确定 HMGB1 对吞噬作用的影响。脂多糖(LPS)用于刺激 HMGB1 从核内易位到细胞质。使用酵母聚糖颗粒来测试巨噬细胞的吞噬功能。我们的研究结果表明,HMGB1 在核内的积累增强了巨噬细胞的吞噬功能。通过与 P53 相互作用,核内 HMGB1 可能仍然留在核内,并减少 P53 对黏着斑激酶(FAK)磷酸化的负性影响。磷酸化 FAK 的增加促进伪足的形成,增强了巨噬细胞的吞噬能力。