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