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| Content Provider | Springer Nature Link |
|---|---|
| Author | Lemaire Ewing, Stéphanie Berthier, Arnaud Royer, Marie Charlotte Logette, Emmanuelle Corcos, Laurent Bouchot, André Monier, Serge Prunet, Céline Raveneau, Magalie Rébé, Cédric Desrumaux, Catherine Lizard, Gérard Néel, Dominique |
| Copyright Year | 2008 |
| Abstract | Oxysterols found in oxidized low-density lipoproteins are probably involved in the appearance of atheroma; some are cytotoxic and some able to induce cytokine secretion. An oxysterol-induced interleukin-8 (IL-8) secretion in human monocytes/macrophages has been previously noticed, but the mechanisms remained unclear. In this paper, we investigated the signaling pathways leading to the induction of IL-8 secretion in monocytic THP-1 cells treated with 7β-hydroxycholesterol, a cytototoxic oxysterol, or with 25-hydroxycholesterol, an oxysterol non-cytotoxic toward this cell line. The oxysterol-induced IL-8 secretion appears to be a calcium-dependent phenomenon as shown by the use of calcium channel blockers, which strongly decreased IL-8 secretion and IL-8 messenger RNA (mRNA) levels. Fluo-3 staining used in flow cytometry and video microscopy revealed an oxysterol-induced Ca2+ influx, varying according to the oxysterol studied, leading to the activation of the MEK/ERK1/2 pathway as demonstrated by Western blot analysis. ERK activation led to an increase of c-fos mRNA and/or an activation of c-fos. Luciferase reporter gene assay using constructs of the human IL-8 gene promoter and Transam assay revealed the involvement of the AP-1 transcription factor in oxysterol-dependent IL-8 secretion. These results demonstrate that oxysterol-induced IL-8 secretion is a calcium-dependent phenomenon involving the MEK/ERK1/2 pathway leading to the activation of IL-8 gene via AP-1 (c-fos). |
| Starting Page | 127 |
| Ending Page | 139 |
| Page Count | 13 |
| File Format | |
| ISSN | 07422091 |
| Journal | Cell Biology and Toxicology |
| Volume Number | 25 |
| Issue Number | 2 |
| e-ISSN | 15736822 |
| Language | English |
| Publisher | Springer Netherlands |
| Publisher Date | 2008-03-04 |
| Publisher Place | Dordrecht |
| Access Restriction | Subscribed |
| Subject Keyword | AP-1 Calcium c-Fos IL-8 Monocytic cells Oxysterols Biochemistry Pharmacology/Toxicology Cell Biology |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Health, Toxicology and Mutagenesis Toxicology |
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