Department of Pharmacology and Experimental Neuroscience, Neuroimmunology and Regenerative Therapy Laboratory, University of Nebraska Medical Center, Omaha, Nebraska, 68198, USA.
Transl Neurodegener. 2012 Jul 31;1(1):15. doi: 10.1186/2047-9158-1-15.
Neurogenesis, including the proliferation, migration and differentiation of neural progenitor cells (NPCs), is impaired in HIV-1 associated dementia (HAD). We previously demonstrated HIV-1-infected macrophages (HIV-MDM) regulate stromal cell-derived factor 1 (SDF-1) production in astrocytes through Interleukin-1β (IL-1β). Chemokines are known to induce NPC migration; however, it remains unclear how chemokines produced in inflammation regulate NPC migration.
The secretion of SDF-1 and Monocyte chemotactic preotein-1 (MCP-1) in astrocytes upon IL-1β stimulation was measured by ELISA assay. Human NPCs were injected parallel along with IL-1β, SDF-1 or MCP-1 intracranially into basal ganglion 1 mm apart in SCID mice, and immunofluorescent staining was used to study the survival and migration of injected human NPCs.
SDF-1 and MCP-1 are secreted by astrocytes upon IL-1β stimulation in a time-dependent manner. Injected human NPCs survived in SCID mice and migrated towards sites of IL-1β, SDF-1 and MCP-1 injection.
In conclusion, chemokines SDF-1 or MCP-1 secreted by astrocytes in the presence of IL-1β injection are attractive to NPCs injected into SCID mouse brains, suggesting that SDF-1 and MCP-1 play important roles in NPC migration during neuroinflammation.
HIV-1 相关性痴呆(HAD)患者的神经发生受到损害,包括神经祖细胞(NPC)的增殖、迁移和分化。我们之前的研究表明,HIV-1 感染的巨噬细胞(HIV-MDM)通过白细胞介素 1β(IL-1β)调节星形胶质细胞中基质细胞衍生因子 1(SDF-1)的产生。趋化因子已知可诱导 NPC 迁移;然而,炎症中产生的趋化因子如何调节 NPC 迁移仍不清楚。
通过 ELISA 检测 IL-1β 刺激后星形胶质细胞中 SDF-1 和单核细胞趋化蛋白-1(MCP-1)的分泌。将人 NPC 平行注入 SCID 小鼠基底节,距离为 1mm,分别与 IL-1β、SDF-1 或 MCP-1 一起注射,然后进行免疫荧光染色,以研究注入的人 NPC 的存活和迁移。
SDF-1 和 MCP-1 是星形胶质细胞在 IL-1β 刺激下以时间依赖的方式分泌的。注入的人 NPC 在 SCID 小鼠中存活,并向 IL-1β、SDF-1 和 MCP-1 注射部位迁移。
总之,IL-1β 注射存在时星形胶质细胞分泌的趋化因子 SDF-1 或 MCP-1 对注入 SCID 小鼠大脑的 NPC 具有吸引力,这表明 SDF-1 和 MCP-1 在神经炎症期间 NPC 迁移中发挥重要作用。