7α-Hydroxycholesterol induces monocyte/macrophage cell expression of interleukin-8 via C5a receptor

Abstract

We investigated effects of 7-oxygenated cholesterol derivatives present in atherosclerotic lesions, 7α-hydroxycholesterol (7αOHChol), 7β-hydroxycholesterol (7βOHChol), and 7-ketocholesterol (7K), on IL-8 expression. Transcript levels of IL-8 and secretion of its corresponding gene product by monocytes/macrophages were enhanced by treatment with 7αOHChol and, to a lesser extent, 7K, but not by 7βOHChol. The 7-oxygenated cholesterol derivatives, however, did not change transcription of the IL-8 gene in vascular smooth muscle cells. 7αOHChol-induced IL-8 gene transcription was inhibited by cycloheximide and Akt1 downregulation, but not by OxPAPC. Expression of C5a receptor was upregulated after stimulation with 7αOHChol, but not with 7K and 7βOHChol, and a specific antagonist of C5a receptor inhibited 7αOHChol-induced IL-8 gene expression in a dose dependent manner. Pharmacological inhibitors of PI3K and MEK almost completely inhibited expression of both IL-8 and cell-surface C5a receptor induced by 7αOHChol. These results indicate that 7-oxygenated cholesterol derivatives have differential effects on monocyte/macrophage expression of IL-8 and C5a receptor and that C5a receptor is involved in 7αOHChol-induced IL-8 expression via PI3K and MEK.

Metabolomics Analysis of Splenic CD19+ B Cells in Mice Chronically Infected With Echinococcus granulosus sensu lato Protoscoleces

“…It has been reported that in atherosclerosis, 7a-Hydroxycholesterol can elicit TLR6-mediated expression of IL-23 by monocytic cells via PI3K/Akt and MAPKs pathways ( 55 ), leading to inflammation via the upregulation of CCL2 and MMP-9 in macrophages ( 56 ). It also causes the enhanced transcript levels of IL-8 and the secretion of its corresponding gene product by monocytes/macrophages ( 57 ), thereby promoting the progression of atherosclerosis. In addition, a decreased level of trimethylamine N-oxide (TMAO) was observed after larval E. granulosus s.l .…”

A Dietary Mixture of Oxysterols Induces In Vitro Intestinal Inflammation through TLR2/4 Activation: The Protective Effect of Cocoa Bean Shells

“…Additionally, only 25-hydroxycholesterol and not 7-KC or 7β-HC, increased Interleukin promoter transcriptional activity by using full-length IL-8 promoter in the same experimental model in the absence of TLR expression [36]. A more recent study showed that the strong induction of IL-8 expression by 7α-HC in THP-1 cells was TLR2 and TLR4 independent [37].…”

Anti-Inflammatory and Proliferative Properties of Luteolin-7-O-Glucoside

“…This information is important since these oxysterols are the major sterols found in human atherosclerotic lesions and presented in oxidized low-density lipoprotein (LDL), where they promote the vascular inflammatory response. Specifically, it was found that 7-ketocholesterol increased extracellular IL-6 protein expression by enhancing secretion from VSMC and that this release of IL-6 resulted being crucial in the onset of cardiovascular disease via its ability to induce adhesion molecules in the endothelium and vascular smooth muscle cells (VSMC) proliferation [50,51]. Continuing to look to hydroxylation phenomena, Figure 6 shows that in the samples treated with LUT-7G, there is an increase of linoleic acid, while its hydroxylated species is not detectable (p < 0.05).…”