Author/Editor		Lakota, Katja; Mrak-Poljšak, Katjuša; Božič, Borut; Tomšič, Matija; Sodin-Šemrl, Snežna
Title		Serum amyloid A activation of human coronary artery endothelial cells exhibits a neutrophil promoting molecular profile
Type		članek
Vol. and No.		Letnik 90
Publication year		2013
Volume		str. 55-63
ISSN		0026-2862 - Microvascular research
Language		eng
Abstract		Serumamyloid A (SAA) has been shown to be an active participant inatherosclerosis and cardiovascular diseases. SAA-stimulated human coronary artery endothelial cells (HCAEC) were reported to release proinflammatory cytokines, chemokines and adhesion molecules; however it remains unclear which putative SAA receptors are present in these cells and how they act. We investigated the effects of inflammatory stimuli on the expression of SAA receptors, signaling pathways and molecular profiles in HCAEC. Methodology/principle findings: HCAEC were cultured in vitro and stimulated with SAA (1000 nM) or IL-1ß (1000 pg/ml). Expression of mRNA was determined byqPCR, and expression and quantification of proteins were assessed by dot array blots and ELISA, respectively. Protein phosphorylationwas determined by dot blot arrays and Western blots. We report that all potential SAA receptors tested (FPR2/ALX, RAGE, TANIS, TLR2, TLR4 and CLA-1/hSR-B1) are expressed in HCAEC. Importantly, IL-1ß or SAA significantly increased solely the expression of the innate immune receptor TLR2. SAA upregulated the phosphorylation of ERK1/2, NF-ŽB (p65, p105) and JNK, aswell as expression/release of IL-6, IL-8, G-CSF, GM-CSF, ICAM-1 and VCAM-1, all potent molecules involved in neutrophil-related activities. A TLR2-dependent positive feedback mechanism of SAA expression was found. Conclusion/significance: SAA stimulated responses in HCAEC target neutrophil rather than monocyte/macrophage activation.
Descriptors		ateroskleroza citokini