Πέμπτη 26 Μαΐου 2016

Monocyte exosomes induce adhesion molecules and cytokines via activation of NF-{kappa}B in endothelial cells [Research]

HIV-infected individuals have activated monocytes with an IFNα phenotype and elevated levels of circulating LPS. These individuals also have a risk of premature cardiovascular disease. The effect of activated monocyte exosomes (Exos) on endothelial cells is unknown. To determine whether Exos from immune-activated monocytes could alter endothelial cell expression and contribute to monocyte/macrophage transmigration and adhesion, we isolated Exos from monocytes stimulated with IFNα, LPS, or a combination of the two (I/L). We show that monocyte Exos contain different inflammatory microRNA cargo depending on stimulation. When LPS Exo or I/L Exo was added to HUVECs, we found a significant increase in adhesion molecule ICAM-1, chemokine ligand (CCL)-2, and cytokine IL-6 mRNAs and proteins compared with cells treated with IFNα Exo or Exos derived from unstimulated monocytes. Inhibition of transcription factor NF-B, a common inflammatory cytokine pathway, prevented induction of CCL2, IL6, and ICAM1. Inhibition of TLR4 resulted in differential blockage of the targets. Our results demonstrate for the first time that primary human monocyte Exos enter endothelial cells and cause dysfunction via the TLR4 and NF-B pathways, which may contribute to heart disease in HIV infection and other diseases involving chronic immune activation.—Tang, N., Sun, B., Gupta, A., Rempel, H., Pulliam, L. Monocyte exosomes induce adhesion molecules and cytokines via activation of NF-B in endothelial cells.



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