Anagliptin alleviates lipopolysaccharide-induced inflammation, apoptosis and endothelial dysfunction of lung microvascular endothelial cells

xlomafota13 shared this article with you from Inoreader Anagliptin alleviates lipopolysaccharide-induced inflammation, apoptosis and endothelial dysfunction of lung microvascular endothelial cells Via Experimental and therapeutic medicine Exp Ther Med. 2021 Dec;22(6):1472. doi: 10.3892/etm.2021.10907. Epub 2021 Oct 22. ABSTRACT It has been reported that dipeptidyl peptidase-4 (DPP4) inhibition protects against acute lung injury (ALI). Anagliptin is a novel selective inhibitor of DPP4 but its role in ALI has not been studied. The present study aimed to investigate the effects of anagliptin on lipopolysaccharide (LPS)-induced human pulmonary microvascular endothelial cell (HPMVEC) injury, as well as its underlying mechanism. HPMVECs were exposed to LPS in the presence or absence of anagliptin co-treatment. MTT assay was used to evaluate cell viability and nitric oxide (NO) production was detected using a commercial kit. DPP4 and pro-inflammatory cytokine expression levels, apoptosis and migration were assessed via reverse transcription-quantitative PCR, western blotting, TUNEL staining and wound healing assay, respectively. Western blot analysis was performed to assess ex pression levels of proteins involved in NF-κB signaling, cell apoptosis and migration, as well as high mobility group box 1 (HMGB1)/receptor for advanced glycation end products (RAGE). LPS decreased cell viability and NO production, but elevated expression of DPP4 in HPMVECs. LPS promoted pro-inflammatory cytokine expression, NF-κB activation and cell apoptosis, but inhibited cell migration and phosphorylated-AKT/endothelial NO synthase expression. Anagliptin co-treatment significantly restored all of these effects. Mechanistically, the upregulation of HMGB1/RAGE expression induced by LPS was markedly blocked by anagliptin. In conclusion, anagliptin alleviated inflammation, apoptosis and endothelial dysfunction in LPS-induced HPMVECs via modulating HMGB1/RAGE expression. These data provide a basis for use of anagliptin in ALI treatment. PMID:34737812 | PMC:PMC8561766 | DOI:10.3892/etm.2021.10907 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.