Endothelin-1 (ET-1) Promotes a Proinflammatory Microglia Phenotype in Diabetic Conditions.

Endothelin-1 (ET-1) Promotes a Proinflammatory Microglia Phenotype in Diabetic Conditions. Can J Physiol Pharmacol. 2020 Mar 02;: Authors: Abdul Y, Jamil S, He L, Li W, Ergul A Abstract Diabetes increases the risk and severity of cognitive impairment, especially after ischemic stroke. It is also known that the activation of ET system is associated with cognitive impairment and microglia around periinfarct area produce ET-1. However, little is known about the effect of ET-1 on microglial polarization, especially under diabetic conditions. We hypothesized that a) ET-1 activates microglia to proinflammatory M-1 like phenotype, and b) Hypoxia/LPS activates the microglial ET system and promotes microglial activation towards M-1 phenotype in diabetic conditions. Microglial cells (C8B4) cultured under normal glucose (25mM) and diabetes-mimicking high glucose (50mM) conditions for 48 hours were stimulated with ET-1, cobalt chloride (200µM) or lipopolysaccharide (100ng/ml) for 24 hours. PPET-1, ET receptor subtypes and M1/M2 marker genes mRNA expression measured by RT-PCR. Secreted ET-1 was measured by ELISA. High dose of ET-1 (1µM), increases the mRNA levels of ET receptors and activates the microglia towards M1 phenotype. Hypoxia or LPS activates the ET system in microglial cells and shifts the microglia towards M1 phenotype in diabetic conditions. These in vitro observations warrant further investigation into the role of ET-1-mediated ac...
Source: Canadian Journal of Physiology and Pharmacology - Category: Drugs & Pharmacology Authors: Tags: Can J Physiol Pharmacol Source Type: research