@Article{macau_mods_00003933, author = {Heimke, Marvin and Lenz, Florian and Rickert, Uta and Lucius, Ralph-Erich and Cossais, Fran{\c{c}}ois}, title = {Anti-Inflammatory Properties of the SGLT2 Inhibitor Empagliflozin in Activated Primary Microglia}, journal = {Cells}, year = {2022}, publisher = {MDPI AG}, address = {Basel}, volume = {11}, number = {19}, pages = {3107}, keywords = {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}, abstract = {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.}, issn = {2073-4409}, doi = {10.3390/cells11193107}, url = {https://macau.uni-kiel.de/receive/macau_mods_00003933}, url = {https://doi.org/10.3390/cells11193107}, url = {http://www.ncbi.nlm.nih.gov/pubmed/36231069}, file = {:https://macau.uni-kiel.de/servlets/MCRFileNodeServlet/macau_derivate_00005102/cells-11-03107.pdf:PDF}, language = {en} }