No abstract

The renin-angiotensin system exerts a profound regulatory effect on the functional features of dendritic cells (DCs), thus suggesting a new target of angiotensin II (Ang II) action in the immune system. This study analyzed whether peroxisome proliferator-activated receptor-gamma (PPAR-c) activation in DCs regulated Ang II-induced activation of DCs and exploited the possible molecular mechanisms, especially focused on the signaling pathways of mitogen-activated protein kinase (MAPK) and nuclear factor-kappa B (NF-jB). Ang II stimulation of human monocyte-derived DCs resulted in an intermediate state of DC maturation and function via modulating the balance of the negative or positive regulation of the signaling pathways of extracellular regulated kinase (ERK), p38 MAPK and NF-jB, but not c-Jun N-terminal kinase (JNK). Moreover, pretreatment of DCs with the PPAR-c agonist pioglitazone reverted these effects of Ang II on DCs via suppression of the MAPK and NF-jB signaling pathways at least in part. Collectively, our data support the notion that PPAR-c activation in human DCs inhibits the activation of DCs induced by Ang II, with which involves the regulation of MAPK and NF-jB signaling pathways. These findings may support the important role of these mediators in the regulation of DC-mediated inflammatory and immunologic processes.

No abstract

Oxidized low-density lipoprotein (oxLDL) has a critical role in the development of atherosclerosis. The participation of oxLDL‑stimulated macrophages has been well‑established in atherosclerosis, however the underlying mechanisms are unclear. Macrophage‑derived exosomes are actively released and are involved in numerous physiological and pathological processes. However, the function of exosomes secreted by oxLDL‑stimulated macrophages in atherosclerosis remains unknown. Exosomes from oxLDL‑treated macrophages and controls were co‑cultured with endothelial cells and the exosomes were taken up by endocytosis. Cell Counting Kit‑8 and tube formation assay results revealed that exosomes derived from oxLDL‑stimulated macrophages reduced the growth and tube formation ability of endothelial cells. Suppression of exosomal secretion by oxLDL‑stimulated macrophages rescued the growth and tube formation ability of endothelial cells. Therefore, the results of the present study indicate that oxLDL‑stimulated macrophages may attenuate the growth and tube formation of endothelial cells, at least in part through exosomal transfer. This may provide novel targets for the development of atherosclerosis therapeutics.