School of Medicine and Life Sciences, Nanjing University of Chinese Medicine, Nanjing 210023, China.
School of Medicine, Hangzhou Normal University, Hangzhou, Zhejiang 310036, China.
Int J Mol Sci. 2019 Feb 3;20(3):659. doi: 10.3390/ijms20030659.
Rapid activation of macrophages plays a central role in eliminating invading bacteria as well as in triggering the inflammatory responses, but how the anti-bacterial and the inflammatory responses are coordinated, in terms of macrophages, is not completely understood. In this study, we demonstrated that () induced the expression of CD200 in murine macrophages in a dose-dependent manner. We found that CD200 significantly suppressed the -induced production of nitric oxide and proinflammatory cytokines in mouse macrophages. Concurrently, the bactericidal capability of macrophages was boosted upon the deletion of CD200. Furthermore, our data demonstrated that p38 mitogen-activated protein kinase (MAPK) was selectively down-regulated by CD200 administration, while enhanced upon CD200 silence in response to staphylococcal infection. The negative effect of CD200 siRNA on NO production in macrophages was largely abrogated upon the inhibition of p38 signaling, implying its critical involvement in this regulation. Together, our data demonstrate that CD200 plays a central role in regulating the inflammatory responses and the anti-bacterial activity of macrophages, at least partially, through suppressing p38 activity.
快速激活巨噬细胞在消除入侵细菌以及引发炎症反应方面发挥着核心作用，但巨噬细胞如何协调抗菌和炎症反应，目前还不完全清楚。在这项研究中，我们证明了 () 以剂量依赖的方式诱导小鼠巨噬细胞中 CD200 的表达。我们发现 CD200 显著抑制了诱导的小鼠巨噬细胞中一氧化氮和促炎细胞因子的产生。同时，巨噬细胞的杀菌能力在 CD200 缺失时增强。此外，我们的数据表明，CD200 给药选择性地下调丝裂原活化蛋白激酶（MAPK）p38 信号通路，而在葡萄球菌感染时，CD200 沉默则增强了该信号通路。p38 信号通路的抑制显著减弱了 CD200 siRNA 对巨噬细胞中 NO 产生的抑制作用，这表明 p38 信号通路在这一调控中起着关键作用。综上所述，我们的数据表明，CD200 通过抑制 p38 活性，在调节巨噬细胞的炎症反应和抗菌活性方面发挥着核心作用，至少部分是通过这种方式。
