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

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 monocyt...

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Autores principales: Cho, Hyok-rae, Son, Yonghae, Kim, Sun-Mi, Kim, Bo-Young, Eo, Seong-Kug, Park, Young Chul, Kim, Koanhoi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5360241/
https://www.ncbi.nlm.nih.gov/pubmed/28323848
http://dx.doi.org/10.1371/journal.pone.0173749
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author Cho, Hyok-rae
Son, Yonghae
Kim, Sun-Mi
Kim, Bo-Young
Eo, Seong-Kug
Park, Young Chul
Kim, Koanhoi
author_facet Cho, Hyok-rae
Son, Yonghae
Kim, Sun-Mi
Kim, Bo-Young
Eo, Seong-Kug
Park, Young Chul
Kim, Koanhoi
author_sort Cho, Hyok-rae
collection PubMed
description 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.
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spelling pubmed-53602412017-04-06 7α-Hydroxycholesterol induces monocyte/macrophage cell expression of interleukin-8 via C5a receptor Cho, Hyok-rae Son, Yonghae Kim, Sun-Mi Kim, Bo-Young Eo, Seong-Kug Park, Young Chul Kim, Koanhoi PLoS One Research Article 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. Public Library of Science 2017-03-21 /pmc/articles/PMC5360241/ /pubmed/28323848 http://dx.doi.org/10.1371/journal.pone.0173749 Text en © 2017 Cho et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Cho, Hyok-rae
Son, Yonghae
Kim, Sun-Mi
Kim, Bo-Young
Eo, Seong-Kug
Park, Young Chul
Kim, Koanhoi
7α-Hydroxycholesterol induces monocyte/macrophage cell expression of interleukin-8 via C5a receptor
title 7α-Hydroxycholesterol induces monocyte/macrophage cell expression of interleukin-8 via C5a receptor
title_full 7α-Hydroxycholesterol induces monocyte/macrophage cell expression of interleukin-8 via C5a receptor
title_fullStr 7α-Hydroxycholesterol induces monocyte/macrophage cell expression of interleukin-8 via C5a receptor
title_full_unstemmed 7α-Hydroxycholesterol induces monocyte/macrophage cell expression of interleukin-8 via C5a receptor
title_short 7α-Hydroxycholesterol induces monocyte/macrophage cell expression of interleukin-8 via C5a receptor
title_sort 7α-hydroxycholesterol induces monocyte/macrophage cell expression of interleukin-8 via c5a receptor
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5360241/
https://www.ncbi.nlm.nih.gov/pubmed/28323848
http://dx.doi.org/10.1371/journal.pone.0173749
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