TY - JOUR
T1 - Dexamethasone inhibits activation of monocytes/macrophages in a milieu rich in 27-oxygenated cholesterol
AU - Kim, Bo Young
AU - Son, Yonghae
AU - Lee, Jeonga
AU - Choi, Jeongyoon
AU - Kim, Chi Dae
AU - Bae, Sun Sik
AU - Eo, Seong Kug
AU - Kim, Koanhoi
N1 - Publisher Copyright:
© 2017 Kim et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2017/12
Y1 - 2017/12
N2 - Molecular mechanisms underlying the decreased number of macrophages and T cells in the arteries of cholesterol-fed-rabbits following dexamethasone administration are unknown. We investigated the possibility that dexamethasone could affect activation of monocytic cells induced by oxygenated derivatives of cholesterol (oxysterols) using THP-1 monocyte/ macrophage cells. 27-Hydroxycholesterol (27OHChol), an oxysterol elevated with hypercholesterolemia, enhanced production of CCL2, known as MCP1, chemokine from monocytes/macrophages and migration of the monocytic cells, but the CCL2 production and the cell migration were reduced by treatment with dexamethasone. Dexamethasone inhibited superproduction of CCL2 induced by 27OHChol plus LPS and attenuated transcription of matrix metalloproteinase 9 as well as secretion of its active gene product induced by 27OHChol. The drug downregulated cellular and surface levels of CD14 and blocked release of soluble CD14 without altering transcription of the gene. Dexamethasone also inhibited expression and phosphorylation of the NF-κB p65 subunit enhanced by 27OHChol. Collectively, these results indicate that dexamethasone inhibits activation of monocytes/ macrophages in response to 27OHChol, thereby leading to decreased migration of inflammatory cells in milieu rich in oxygenated derivatives of cholesterol.
AB - Molecular mechanisms underlying the decreased number of macrophages and T cells in the arteries of cholesterol-fed-rabbits following dexamethasone administration are unknown. We investigated the possibility that dexamethasone could affect activation of monocytic cells induced by oxygenated derivatives of cholesterol (oxysterols) using THP-1 monocyte/ macrophage cells. 27-Hydroxycholesterol (27OHChol), an oxysterol elevated with hypercholesterolemia, enhanced production of CCL2, known as MCP1, chemokine from monocytes/macrophages and migration of the monocytic cells, but the CCL2 production and the cell migration were reduced by treatment with dexamethasone. Dexamethasone inhibited superproduction of CCL2 induced by 27OHChol plus LPS and attenuated transcription of matrix metalloproteinase 9 as well as secretion of its active gene product induced by 27OHChol. The drug downregulated cellular and surface levels of CD14 and blocked release of soluble CD14 without altering transcription of the gene. Dexamethasone also inhibited expression and phosphorylation of the NF-κB p65 subunit enhanced by 27OHChol. Collectively, these results indicate that dexamethasone inhibits activation of monocytes/ macrophages in response to 27OHChol, thereby leading to decreased migration of inflammatory cells in milieu rich in oxygenated derivatives of cholesterol.
UR - https://www.scopus.com/pages/publications/85038245410
U2 - 10.1371/journal.pone.0189643
DO - 10.1371/journal.pone.0189643
M3 - Journal article
C2 - 29236764
AN - SCOPUS:85038245410
SN - 1932-6203
VL - 12
JO - PLoS ONE
JF - PLoS ONE
IS - 12
M1 - e0189643
ER -