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Empagliflozin Inhibits IL-1β-Mediated Inflammatory Response in Human Proximal Tubular Cells.
- Source :
-
International journal of molecular sciences [Int J Mol Sci] 2021 May 11; Vol. 22 (10). Date of Electronic Publication: 2021 May 11. - Publication Year :
- 2021
-
Abstract
- SGLT2 inhibitor-related nephroprotection is-at least partially-mediated by anti-inflammatory drug effects, as previously demonstrated in diabetic animal and human studies, as well as hyperglycemic cell culture models. We recently presented first evidence for anti-inflammatory potential of empagliflozin (Empa) under normoglycemic conditions in human proximal tubular cells (HPTC) by demonstrating Empa-mediated inhibition of IL-1β-induced MCP-1/CCL2 and ET-1 expression on the mRNA and protein level. We now add corroborating evidence on a genome-wide level by demonstrating that Empa attenuates the expression of several inflammatory response genes in IL-1β-induced (10 ng/mL) normoglycemic HPTCs. Using microarray-hybridization analysis, 19 inflammatory response genes out of >30.000 human genes presented a consistent expression pattern, that is, inhibition of IL-1β (10 ng/mL)-stimulated gene expression by Empa (500 nM), in both HK-2 and RPTEC/TERT1 cells. Pathway enrichment analysis demonstrated statistically significant clustering of annotated pathways (enrichment score 3.64). Our transcriptomic approach reveals novel genes such as CXCL8/IL8, LOX, NOV, PTX3 , and SGK1 that might be causally involved in glycemia-independent nephroprotection by SGLT2i.
- Subjects :
- Gene Expression Profiling
Humans
Inflammation chemically induced
Inflammation pathology
Kidney Tubules, Proximal drug effects
Kidney Tubules, Proximal metabolism
Sodium-Glucose Transporter 2 Inhibitors pharmacology
Benzhydryl Compounds pharmacology
Gene Expression Regulation drug effects
Glucosides pharmacology
Inflammation immunology
Interleukin-1beta pharmacology
Kidney Tubules, Proximal immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1422-0067
- Volume :
- 22
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- International journal of molecular sciences
- Publication Type :
- Academic Journal
- Accession number :
- 34064989
- Full Text :
- https://doi.org/10.3390/ijms22105089