@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}
}