000K utf8 1100 $c2022 1500 eng 2050 urn:nbn:de:gbv:8:3-2023-00610-2 2051 10.3390/cells11193107 3000 Heimke, Marvin 3010 Cossais, François 3010 Lenz, Florian 3010 Lucius, Ralph-Erich 3010 Rickert, Uta 4000 Anti-Inflammatory Properties of the SGLT2 Inhibitor Empagliflozin in Activated Primary Microglia [Heimke, Marvin] 4209 Sodium-glucose cotransporter 2 (SGLT2) inhibitors, including empagliflozin, are routinely used as antidiabetic drugs. Recent studies indicate that beside its beneficial effects on blood glucose level, empagliflozin may also exert vascular anti-inflammatory and neuroprotective properties. In the brain, microglia are crucial mediators of inflammation, and neuroinflammation plays a key role in neurodegenerative disorders. Dampening microglia-mediated inflammation may slow down disease progression. In this context, we investigated the immunomodulatory effect of empagliflozin on activated primary microglia. As a validated experimental model, rat primary microglial cells were activated into a pro-inflammatory state by stimulation with LPS. The influence of empagliflozin on the expression of pro-inflammatory mediators (NO, Nos2, IL6, TNF, IL1B) and on the anti-inflammatory mediator IL10 was assessed using quantitative PCR and ELISA. Further, we investigated changes in the activation of the ERK1/2 cascade by Western blot and NFkB translocation by immunostaining. We observed that empagliflozin reduces the expression of pro- and anti-inflammatory mediators in LPS-activated primary microglia. These effects might be mediated by NHE-1, rather than by SGLT2, and by the further inhibition of the ERK1/2 and NFkB pathways. Our results support putative anti-inflammatory effects of empagliflozin on microglia and suggest that SGLT2 inhibitors may exert beneficial effects in neurodegenerative disorders. 4950 https://doi.org/10.3390/cells11193107$xR$3Volltext$534 4950 https://nbn-resolving.org/urn:nbn:de:gbv:8:3-2023-00610-2$xR$3Volltext$534 4961 https://macau.uni-kiel.de/receive/macau_mods_00003933 5051 610 5550 Animals 5550 Anti-Inflammatory Agents 5550 Benzhydryl Compounds 5550 Blood Glucose 5550 Empagliflozin 5550 ERK1/2 5550 Glucosides 5550 Hypoglycemic Agents 5550 IL6 5550 Inflammation 5550 Inflammation Mediators 5550 Interleukin-10 5550 Interleukin-6 5550 Lipopolysaccharides 5550 Microglia 5550 Microglia 5550 Neurodegeneration 5550 neuroinflammation 5550 NF-kappa B 5550 NHE-1 5550 Rats 5550 Sglt1 5550 Sglt2 5550 Sodium 5550 Sodium-Glucose Transporter 2 5550 Sodium-Glucose Transporter 2 Inhibitors 5550 TNF