| 초록 |
Chronic kidney disease (CKD) patients often experience vitamin D deficiency, which can exacerbate vascular calcification and inflammation, contributing to vascular stenosis, particularly in hemodialysis patients. This study investigates the role of vitamin D in modulating macrophage function when exposed to indoxyl sulfate (IS), a known uremic toxin. We used THP-1 cells pretreated with 30 nM vitamin D (1,25(OH)₂D₃) for varying durations (12, 24, 36, and 48 hours), followed by exposure to IS at concentrations of 125 and 250 μg/mL for 24 hours. We observed morphological changes via microscopy and assessed macrophage differentiation using real-time PCR to analyze M1 markers (CD86, iNOS, TNF-α, IL-6, IL-1β) and M2 markers (CD163, Arginase-1, IL-10). Functional changes were evaluated by measuring inflammatory markers (TNF-α, IL-6, MCP-1) through real-time PCR. We also assessed changes in cholesterol metabolism using a cholesterol efflux assay, real-time PCR (ABCA1, ABCG1), and Oil Red O staining to visualize foam cell formation. Vitamin D pretreatment downregulated M1 markers, thus attenuating IS-induced inflammatory responses while upregulating M2 markers, enhancing anti-inflammatory responses. Vitamin D also suppressed IS-induced TNF-α, IL-6, and MCP-1 expression, mitigating inflammation. It also increased the expression of ABCA1 and ABCG1, promoting cholesterol efflux and reducing foam cell formation, indicating its role in counteracting IS-induced lipid accumulation and inflammation in macrophages. These findings indicate that vitamin D may significantly alleviate IS-induced vascular complications in CKD by regulating macrophage function. This highlights the potential of vitamin D as a therapeutic strategy to prevent vascular stenosis in hemodialysis patients. |