English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

Objective— Modified lipoproteins induce inflammatory reactions in the atherosclerotic arterial wall. We have previously found that macrophages in atherosclerotic lesions secrete lysosomal hydrolases that can modify low-density-lipoprotein (LDL) in vitro to generate “hydrolase-modified LDL” (H-LDL). Here, we studied whether H-LDL exerts inflammatory effects on cultured human macrophages.Methods and Results— Using cytokine cDNA arrays, we found that H-LDL induced expression of IL-8, but not of the anti-inflammatory cytokines IL-10 and transforming growth factor (TGF)-β, in human monocyte-derived macrophages. H-LDL induced rapid phosphorylation of the p38 mitogen-activated protein kinase (MAPK), nuclear translocation of 2 transcription factors, nuclear factor κB (NF-κB) and activator protein 1 (AP-1), and time-dependent secretion of IL-8 from the macrophages. Inhibition of MAPKs and of transcription factors showed that p38 MAPK and NF-κB, but not ERK1/2, JNK, or AP-1, were crucial for the H-LDL–induced IL-8 secretion from the macrophages.Conclusions— The results show that by activating p38 MAPK and NF-κB, macrophage hydrolases modify LDL into biologically active particles capable of triggering the secretion of IL-8 in macrophages. Thus, activated hydrolase-secreting macrophages in atherosclerotic lesions may sustain a proatherogenic extracellular environment by hydrolyzing LDL and triggering it to act in an autocrine or paracrine fashion to induce IL-8 secretion by the plaque macrophages.

arteriosclerosis, thrombosis, and vascular biology

Low-Density Lipoprotein Modified by Macrophage-Derived Lysosomal Hydrolases Induces Expression and Secretion of IL-8 Via p38 MAPK and NF-κB by Human Monocyte-Derived Macrophages