Bacteriophage-derived dsRNA of natural origin alters functional profile of rat microglial cells exposed to hypoxia in vitro: Evaluation of metabolic and phenotypic markers

Abstract

BackgroundMicroglial cells (MC) are thought to be major innate immune cells in the central nervous system. Hypoxia can cause pro- and anti-inflammatory MC activation. Toll-like receptors (TLRs) play an important role in the regulation of microglia activity and can skew metabolic profile of resting and activated MC. However, the data concerning the effect of TLR agonists on metabolic profile of MC activated by hypoxia are controversial and sparse. Larifan is a pharmaceutical product containing a heterogeneous population of natural origin double-stranded RNA (dsRNA). This study was aimed to investigate the effect of the treatment with Larifan on functional profile of rat MC exposed to hypoxia in vitro. MethodsRat MC were cultured under normoxic (21% O2) or hypoxic (3% O2) conditions for 24 h. After this, cells were treated with Larifan (200 μg/mL) for 18 h. To characterize MC functional profile, reactive oxygen species (ROS) generation, phagocytic activity, arginine metabolism as well as CD206 and CD14 expression were examined. ResultsHypoxic MC were characterized by sharply increased ROS generation, moderately boosted phagocytic activity, arginine metabolism was skewed towards increased arginase activity, CD14+ and CD206+ cell fractions were higher than those in normoxic cells. Treatment MC with Larifan resulted in further increase ROS generation along with the decrease of phagocytic activity that is characteristic for the acquisition of antigen-presenting properties by these cells. The level of CD206 expression was lowered in treated hypoxic MC. ConclusionLarifan promotes transition of hypoxic MC to the state of mature pro-inflammatory APC in vitro.