小胶质细胞
CX3CR1型
神经炎症
趋化因子
神经保护
受体
兴奋剂
细胞生物学
脂多糖
趋化因子受体
化学
刺激
药理学
生物
免疫学
神经科学
炎症
生物化学
作者
Michela Perrone,Mario Pagano,Carmela Belardo,Flavia Ricciardi,Federica Ricciardi,Antimo Fusco,Maria Consiglia Trotta,Rosmara Infantino,Francesca Gargano,Andrea Parente,Rosa Giacca,Gorizio Pieretti,Livio Luongo,Sabatino Maione,Serena Boccella,Francesca Guida
标识
DOI:10.1016/j.neuropharm.2023.109456
摘要
Following insults or injury, microglia cells are activated contributing to the cytotoxic response or by promoting an immune-mediated damage resolution. Microglia cells express HCA2R, a hydroxy carboxylic acid (HCA) receptor, which has been shown to mediate neuroprotective and anti-inflammatory effects. In this study we found that HCAR2 expression levels were increased in cultured rat microglia cells after Lipopolysaccharide (LPS) exposure. In a similar fashion, the treatment with MK 1903, a potent full agonist of HCAR2, increased the receptor protein levels. Moreover, HCAR2 stimulation prevented i) cells viability ii) morphological activation iii) pro/anti-inflammatory mediators production in LPS-treated cells. Likewise, HCAR2 stimulation reduced the proinflammatory mediators mRNA expression induced by neuronal chemokine fractalkine (FKN), a neuronal derived chemokine activating its unique receptor, chemokine receptor 1 (CX3CR1) on microglia surface. Interestingly, electrophysiological recordings in vivo revealed that MK1903 was able to prevent the increase of the nociceptive neurons (NS) firing activity mediated by the spinal FKN application in healthy rats. Collectively, our data demonstrate that HCAR2 is functionally expressed in microglia, by showing its capability to shift microglia toward an anti-inflammatory phenotype. Moreover, we indicated the contribute of HCAR2 in the FKN signaling and suggested a possible HCAR2/CX3CR1 functional interaction. This study paves the way for further investigations aimed at understanding the role HCAR2 as potential target in neuroinflammation-based CNS disorders. This article is part of the Special Issue on "The receptor-receptor interaction as a new target for therapy".
科研通智能强力驱动
Strongly Powered by AbleSci AI