Department of Physiology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250012, PR China.
Department of Physiology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250012, PR China; Department of Medical Psychology and Ethics, School of Basic Medicine Sciences, Cheeloo College of Medicine, Shandong University, Jinan, 250012, Shandong, PR China.
Biomed Pharmacother. 2021 Mar;135:111207. doi: 10.1016/j.biopha.2020.111207. Epub 2021 Feb 1.
We previously reported that L-Cysteine, HS donor, remarkably attenuated neuroinflammation following hypoxia-ischemia (HI) brain injury in neonatal mice. However, its anti-inflammatory mechanism for HI insult is still unknown. The study focus on the effects of L-Cysteine on immune cell populations, Ca mobilization and phagocytosis after neonatal HI. We found that L-Cysteine treatment skewed CD11b/CD45 microglia and CD11b/CD45 brain monocytes/macrophages towards a more anti-inflammatory property 72 h after HI-injured brain. Moreover, L-Cysteine treatment reduced cerebral infiltration of CD4 T cells 7 days following HI insult. Furthermore, CD4 T cell subset analysis revealed that L-Cysteine treatment decreased Th1 and Th2 counts, while increased Th17/Th2 ratio. Moreover, L-Cysteine treatment suppressed LPS-induced cytosolic Ca and LPS-stimulated phagocytosis in primary microglia. The anti-inflammatory effect of L-Cysteine was associated with improving neurobehavioral impairment following HI insult. Our results demonstrate L-Cysteine treatment suppressed the invasion of peripheral immune cells, increasing [Ca]i and excessive phagocytosis to improve neurobehavioral deficits following hypoxia-ischemia injury in neonatal mice by HS release.
我们之前曾报道，HS 供体 L-半胱氨酸可显著减轻新生鼠缺氧缺血（HI）脑损伤后的神经炎症。然而，其对 HI 损伤的抗炎机制尚不清楚。本研究重点研究 L-半胱氨酸对新生 HI 后免疫细胞群、钙动员和吞噬作用的影响。我们发现，L-半胱氨酸处理使 HI 损伤后 72 小时的 CD11b/CD45 小胶质细胞和 CD11b/CD45 脑单核细胞/巨噬细胞向更具抗炎特性的方向偏移。此外，L-半胱氨酸处理可减少 HI 损伤后 7 天大脑中 CD4 T 细胞的浸润。此外，CD4 T 细胞亚群分析表明，L-半胱氨酸处理减少了 Th1 和 Th2 的计数，同时增加了 Th17/Th2 的比值。此外，L-半胱氨酸处理抑制了原代小胶质细胞中 LPS 诱导的胞质 Ca 和 LPS 刺激的吞噬作用。L-半胱氨酸的抗炎作用与改善 HI 损伤后的神经行为损伤有关。我们的结果表明，L-半胱氨酸处理通过 HS 释放可抑制外周免疫细胞的浸润，增加[Ca]i 和过度吞噬，从而改善新生鼠缺氧缺血损伤后的神经行为缺陷。
