Abstract
Serum amyloid A (SAA) is an acute-phase protein with important, pathogenic role in the development of atherosclerosis. Since dysfunctional endothelium represents a key early step in atherogenesis, we aimed to determine whether induced human coronary artery endothelial cells (HCAEC) modulate SAA1/2/4 expression and influence intracellular location and intercellular transport of SAA1. HCAEC were stimulated with 1 ng/ml IL-1β, 10 ng/ml IL-6, and/or 1 μM dexamethasone for 24 h. QPCR, Western blots, ELISA, and immunofluorescent labeling were performed for detection of SAA1/2/4 mRNA and protein levels, respectively. In SAA1 transport experiments, FITC- or Cy3-labeled SAA1 were added to HCAEC separately, for 24 h, followed by a combined incubation of SAA1-FITC and SAA1-Cy3 positive cells, with IL-1β and analysis by flow cytometry. IL-1β upregulated SAA1 (119.9-fold, p < 0.01) and SAA2 (9.3-fold; p < 0.05) mRNA expression levels, while mRNA expression of SAA4 was not affected. Intracellular SAA1 was found mainly as a monomer, while SAA2 and SAA4 formed octamers as analyzed by Western blots. Within HCAEC, SAA1/2/4 located mostly to the perinuclear area and tunneling membrane nanotubes. Co-culturing of SAA1-FITC and SAA1-Cy3 positive cells for 48 h showed a significantly higher percentage of double positive cells in IL-1β-stimulated (mean ± SD; 60 ± 4%) vs. non-stimulated cells (48 ± 2%; p < 0.05). IL-1β induces SAA1 expression in HCAEC and promotes its intercellular exchange, suggesting that direct communication between cells in inflammatory conditions could ultimately lead to faster development of atherosclerosis in coronary arteries.
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The study was supported by the Slovenian Research Agency ARRS within the National Research Program #P30314.
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TK, SSS, and AE designed the experiments, acquired and analyzed the data, and wrote the manuscript. TK, KMP, and KL performed the experiments. KL, SČ, and SSS coordinated the study. All authors participated in critical discussion of the data and drafting the manuscript.
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Kuret, T., Sodin-Šemrl, S., Mrak-Poljšak, K. et al. Interleukin-1β Induces Intracellular Serum Amyloid A1 Expression in Human Coronary Artery Endothelial Cells and Promotes its Intercellular Exchange. Inflammation 42, 1413–1425 (2019). https://doi.org/10.1007/s10753-019-01003-3
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DOI: https://doi.org/10.1007/s10753-019-01003-3