| Author/Editor | Kuret, Tadeja; Sodin-Šemrl, Snežna; Mrak Poljšak, Katjuša; Čučnik, Saša; Lakota, Katja; Erman, Andreja | |
| Title | Interleukin-1[beta] induces intracellular serum amyloida1 expression in human coronary artery endothelial cellsand promotes its intercellular exchange | |
| Type | članek | |
| Vol. and No. | Letnik 42, št. 4 | |
| Publication year | 2019 | |
| Volume | str. 1413-1425 | |
| ISSN | 0360-3997 - Inflammation | |
| Language | eng | |
| 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-1[beta], 10 ng/ml IL-6, and/or 1 [micro]M 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-1[beta] and analysis by flow cytometry. IL-1[beta] 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-1[beta]-stimulated (mean +- SD; 60+-4%) vs. non-stimulated cells (48+-2%; p<0.05). IL-1[beta] 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. | |
| Keywords | atherosclerosis IL-1beta human coronary artery endothelial cells ateroskleroza IL-1beta endotelne celice človeške koronarne arterije |