PT Journal AU Heimke, M Lenz, F Rickert, U Lucius, R Cossais, F TI Anti-Inflammatory Properties of the SGLT2 Inhibitor Empagliflozin in Activated Primary Microglia SO Cells PY 2022 BP 3107 VL 11 IS 19 PU MDPI AG DI 10.3390/cells11193107 WP https://macau.uni-kiel.de/receive/macau_mods_00003933 LA en DE Microglia; Animals; Rats; Inflammation; Sodium; Benzhydryl Compounds; Lipopolysaccharides; Glucosides; Blood Glucose; NF-kappa B; Anti-Inflammatory Agents; Inflammation Mediators; Interleukin-6; Interleukin-10; Hypoglycemic Agents; Sodium-Glucose Transporter 2; Sodium-Glucose Transporter 2 Inhibitors; TNF; NHE-1; ERK1/2; Neurodegeneration; IL6; neuroinflammation; Sglt2; Sglt1; Empagliflozin SN 2073-4409 AB Sodium-glucose cotransporter 2 (SGLT2) inhibitors, including empagliflozin, are routinely used as antidiabetic drugs. Recent studies indicate that beside its beneficial effects on blood glucose level, empagliflozin may also exert vascular anti-inflammatory and neuroprotective properties. In the brain, microglia are crucial mediators of inflammation, and neuroinflammation plays a key role in neurodegenerative disorders. Dampening microglia-mediated inflammation may slow down disease progression. In this context, we investigated the immunomodulatory effect of empagliflozin on activated primary microglia. As a validated experimental model, rat primary microglial cells were activated into a pro-inflammatory state by stimulation with LPS. The influence of empagliflozin on the expression of pro-inflammatory mediators (NO, Nos2, IL6, TNF, IL1B) and on the anti-inflammatory mediator IL10 was assessed using quantitative PCR and ELISA. Further, we investigated changes in the activation of the ERK1/2 cascade by Western blot and NFkB translocation by immunostaining. We observed that empagliflozin reduces the expression of pro- and anti-inflammatory mediators in LPS-activated primary microglia. These effects might be mediated by NHE-1, rather than by SGLT2, and by the further inhibition of the ERK1/2 and NFkB pathways. Our results support putative anti-inflammatory effects of empagliflozin on microglia and suggest that SGLT2 inhibitors may exert beneficial effects in neurodegenerative disorders. PI Basel ER