Oxidized low-density lipoprotein stimulates dendritic cells maturation via LOX-1-mediated MAPK/NF-κB pathway

Abstract

Dendritic cells (DCs) play a crucial role as central orchestrators of immune system response in atherosclerosis initiation and progression. Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) is involved in the immune maturation of DCs, but the underlying mechanisms remain unclear. We isolated mouse bone marrow progenitors and stimulated them with granulocyte-macrophage colony-stimulating factor and interleukin (IL)-4 to induce immature DCs. We then treated DCs with oxidized low-density lipoprotein (oxLDL) to induce maturation. LOX-1 siRNA was used to investigate the modulation of LOX-1 on the development of DCs and the underlying signal pathways. CD11c-positive DCs were successfully derived from mouse bone marrow progenitors. OxLDL promoted the expressions of DCs maturation markers and pro-inflammatory cytokines. OxLDL also upregulated LOX-1 expression and activated MAPK/NF-κB pathways. LOX-1 siRNA could attenuate the expression of MAPK/NF-κB pathways and inflammatory cytokines. In conclusion, oxLDL induced the maturation of DCs via LOX-1-mediated MAPK/NF-κB pathway, which contributed to the initiation and progression of atherosclerosis.

Small interfering RNA-induced silencing lncRNA PVT1 inhibits atherosclerosis via inactivating the MAPK/NF-κB pathway

“…NF-κB is considered as a pro-atherogenic factor, mainly due to its regulatory effect on pro-inflammatory proteins linked to AS, thus NF-κB inhibition could attenuate the pathogenesis of AS [ 37 ]. The LOX-1/p38 MAPK pathway participates in endothelial dysfunction in AS [ 38 ]. PVT1 was upregulated in the myocardial tissues of sepsis rats, activated the MAPK/NF-κB pathway, and thus inhibited cardiac function and promoted the secretion of inflammatory factors [ 18 ].…”

The Role of C-Type Lectin Receptor Signaling in the Intestinal Microbiota-Inflammation-Cancer Axis

“…The lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) is expressed by vascular endothelial cells ( 168 ), vascular smooth muscle cells, cardiomyocytes, adipocytes, platelets, monocytes, macrophages, DCs, B cells, chondrocytes ( 169 ) and intestinal cells ( 170 ) ( Table 1 ), and function as a scavenger receptor ( 171 ). The low expression of LOX-1 under physiological conditions can be up-regulated by many diseases-related stimuli, such as cytokines (e.g., TGF-β1 ( 172 ), TNF-α ( 173 )), oxidized low-density lipoprotein (oxLDL) ( 174 , 175 ), angiotensin II ( 176 ), endothelin ( 177 ), asymmetric dimethylarginine ( 178 ). There is no known ITAM or ITIM in LOX-1 cytoplasmic tail, but LOX-1 can also mediate NF-κB pathway, thus implying LOX-1 utilizes other molecules for intracellular signaling transduction, which needs further elucidation ( 27 ).…”

“…Furthermore, Ox-LDL can bind LOX-1 and there is considerable evidence for their pathogenic role in atherosclerosis. Based on LOX-1 mediated MAPK/NF-κB pathway activation, Ox-LDL elevates the levels of LOX-1, promotes the maturation and differentiation of DCs and induces a proinflammatory cytokine profile ( 174 , 175 ). Heat shock proteins(HSP) also bind to LOX-1, and anti-LOX-1 antibody impedes such ligation thus inhibiting HSP-induced antigen cross-presentation ( 40 ).…”