Regulatory Effects of Antioxidants on Indoxyl Sulfate-Enhanced Intracellular Oxidation and Impaired Phagocytic Activity in Differentiated U937 Human Macrophage Cells.
Wakana IwamotoTomohiro IkedaHirotaka NishikawaMasashi HiranoHideki KinoshitaMasateru OnoKatsuhisa KurogiYoichi SakakibaraMasahito SuikoShin YasudaPublished in: Bioscience, biotechnology, and biochemistry (2024)
Indoxyl sulfate (IS), a uremic toxin, is a physiologically active sulfated metabolite, specifically in kidney failure patients. Our previous studies have shown that IS downregulates phagocytic immune function in a differentiated HL-60 human macrophage cell model. However, it remains unclear whether IS exerts similar effects on macrophage function in other cell types or in lipopolysaccharide (LPS)-sensitive immune cell models. Therefore, this study aimed to investigate the effects of IS on intracellular oxidation levels and phagocytic activity in a differentiated U937 human macrophage cell model, both in the absence and presence of LPS. Our results demonstrated that IS significantly increases intracellular oxidation levels and decreases phagocytic activity, particularly in cells activated by LPS. Furthermore, we found that 2-acetylphenothiazine, an NADH oxidase inhibitor, attenuates the effects of IS in LPS-activated macrophage cells. Representative antioxidants, trolox, α-tocopherol, and ascorbic acid, significantly mitigated the effects of IS on the macrophages responding to LPS.
Keyphrases
- inflammatory response
- induced apoptosis
- endothelial cells
- adipose tissue
- cell cycle arrest
- anti inflammatory
- single cell
- cell therapy
- escherichia coli
- pluripotent stem cells
- ejection fraction
- hydrogen peroxide
- reactive oxygen species
- stem cells
- signaling pathway
- endoplasmic reticulum stress
- toll like receptor
- lps induced
- transcription factor
- cell death
- nitric oxide
- prognostic factors
- cross sectional
- patient reported outcomes