Abstract
Inflammation is intimately involved in the pathogenesis of diabetic kidney disease. Inhibition of SGLT-2 by a specific class of drugs, gliflozins, has been shown to reduce inflammation and attenuate the progression of diabetic nephropathy, in addition to its main effect of inhibiting renal glucose reabsorption. We used highly purified human renal proximal tubular epithelial cells (PTCs) as an in vitro model to study the cellular response to a diabetic (high glucose) and inflammatory (cytokines) microenvironment and the effect of gliflozins. In this context, we investigated the influence of SGLT-2 inhibition by empa- and dapagliflozin (500 nM) on the expression of pro-inflammatory factors (IL-1β, IL-6, TNF-α, MCP-1, and ICAM-1). The results clearly indicate an anti-inflammatory effect of both gliflozins. Although induced expression of the four cytokines was only slightly attenuated, there was a clear effect on the expression of the adhesion molecule ICAM-1, a master regulator of cellular responses in inflammation and injury resolution. The induced expression of ICAM-1 mRNA was significantly reduced by approximately 13.5% by empagliflozin and also showed an inhibitory trend with dapagliflozin. However, induced ICAM-1 protein expression was significantly inhibited from 24.71 ± 1.0 ng/mL to 18.81 ± 3.9 (empagliflozin) and 19.62 ± 2.1 ng/mL (dapagliflozin). In conclusion, an additional anti-inflammatory effect of empa- and dapagliflozin in therapeutically observed concentrations was demonstrated in primary human PTCs in vitro.
Funder
Dr. Hans Messer Stiftung, Bad Soden, Germany
Subject
Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis
Reference53 articles.
1. Pharmacological aspects of the safety of gliflozins;Faillie;Pharmacol. Res.,2017
2. Role of the kidney in normal glucose homeostasis and in the hyperglycaemia of diabetes mellitus: Therapeutic implications;Gerich;Diabet. Med.,2010
3. Tentolouris, A., Vlachakis, P., Tzeravini, E., Eleftheriadou, I., and Tentolouris, N. (2019). SGLT2 Inhibitors: A Review of Their Antidiabetic and Cardioprotective Effects. Int. J. Environ. Res. Public Health, 16.
4. Diabetic Kidney Disease: Challenges, Progress, and Possibilities;Alicic;Clin. J. Am. Soc. Nephrol.,2017
5. Tofogliflozin, a Highly Selective Inhibitor of SGLT2 Blocks Proinflammatory and Proapoptotic Effects of Glucose Overload on Proximal Tubular Cells Partly by Suppressing Oxidative Stress Generation;Ishibashi;Horm. Metab. Res.,2016
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