Bone Marrow Mesenchymal Stem Cells Alleviate Extracellular Kynurenine Levels, as Detected by High-Performance Liquid Chromatography

Abstract

Endothelial cell dysfunction plays an important role in the occurrence and development of sepsis, which is a consequence of the interaction between coagulation and inflammation. Kynurenine (KYN) is an endothelium-derived relaxing factor that makes a large contribution to sepsis pathophysiology. In this study, we investigated the influence of bone marrow mesenchymal stem cells (BMSCs) on KYN production by cultured endothelial cells. KYN and tryptophan (TRP) concentrations in cell supernatants were simultaneously measured with a high-performance liquid chromatography (HPLC) system equipped with a fluorescence detector (FLD) and an ultraviolet detector (UVD). Our results revealed that lipopolysaccharide-stimulated endothelial cells produced more KYN, which was accompanied by a parallel decrease in TRP. When co-cultured with BMSCs, KYN and TRP production were significantly decreased compared to lipopolysaccharide (LPS)-induction alone. Our results suggest that BMSCs can attenuate endothelial cell damage by decreasing KYN as detected with HPLC. This method is the first to be capable of capturing functional changes in the cells and is simple, fast, and suitable for cellular level research purposes.

Interleukin-17A is associated with flow-mediated dilation and interleukin-4 with carotid plaque in persons with HIV

“…PWH on efavirenz have been shown to have higher kynurenine-tryptophan ratios due to decreased Kyn pathway activity [48]. Kyn pathway activity can suppress IL-17A expression and mediate arterial dilation under conditions of systemic inflammation due to infection [49]. Suppression of the Kyn pathway in patients on efavirenz could therefore decrease FMD and increase IL- 17A, which might explain some of the differences between PWH and HIV-negative.…”