Cholesterol-Induced Impact on Murine Macrophage Responsiveness Involves down-Regulation of Mevalonate Pathway

Yakov Sh. Schwartz; Olga M. Dolganova; Sergey V. Cheresiz

doi:doi:10.11648/j.ab.20140201.14

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Cholesterol-Induced Impact on Murine Macrophage Responsiveness Involves down-Regulation of Mevalonate Pathway

Yakov Sh. Schwartz, Olga M. Dolganova, Sergey V. Cheresiz

Published in Advances in Biochemistry (Volume 2, Issue 1)

Received: 8 February 2014 Published: 10 March 2014

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Abstract

Free cholesterol (Ch) and its oxidative derivatives, oxysterols, are often accumulated in macrophages during chronic inflammation and atherogenesis. The effects of Ch and oxysterols on the balance of pro- and anti-inflammatory cytokines in inflammatory response and the role of mevalonate pathway in the effects of these sterols are studied poorly. We studied the effects of cholesterol, oxysterols, atorvastatin, and mevalonic acid on the LPS-induced TNF-α, IL-10, and TGF-β1 production in macrophage cell culture. The study was carried out in murine peritoneal macrophages preincubated for 4 h with Ch (5 µg/mL), 25-hydroxycholesterol (25-OH-Ch) (5 µg/mL), 7-keto-Ch (5 µg/mL), farnesol (10 µM), or atorvastatin (5 µmol/mL) in the presence or absence of 1 mM of mevalonate. The cells were further incubated in the presence or absence of E. coli 0111:B4 lipopolysaccharide (LPS) for 24 h, and cytokine concentrations in incubation media were determined. Macrophages preincubation with Ch, 25-OH-Ch, or atorvastatin decreased LPS-induced TNF-α production in cell cultures, while supplementation of preincubation medium with mevalonic acid abrogated the effects of atorvastatin and Ch. The Ch, 25-OH-Ch, 7-keto-Ch and atorvastatin significantly reduced IL-10 production by LPS–stimulated macrophages, while farnesol had no effect. Supplementation of Ch or atorvastatin-containing preincubation medium with mevalonate restored IL-10 production. The TGF-β1 production was significantly enhanced by the presence of Ch or atorvastatin in preincubation medium as compared to the control level in non-treated macrophages, while 25-OH-Ch or farnesol decreased profoundly TGF-β1 production. Mevalonate abrogated the effect of Ch or atorvastatin but not of 25-OH-Ch or farnesol. These results allow to conclude, that Ch is able to promote anti-inflammatory and fibrogenic macrophage response, which is connected, at least in part, with the deficiency of mevalonate pathway intermediates, particularly to the deficiency of farnesol, whereas hydroxysterols produce tolerogenic, but not fibrogenic effect, independently of mevalonate pathway.

Published in	Advances in Biochemistry (Volume 2, Issue 1)
DOI	10.11648/j.ab.20140201.14
Page(s)	24-28
Creative Commons	This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited.
Copyright	Copyright © The Author(s), 2014. Published by Science Publishing Group

Keywords

Macrophage, Cytokines, Cholesterol, Oxysterols, Mevalonate Pathway

References

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APA Style

Yakov Sh. Schwartz, Olga M. Dolganova, Sergey V. Cheresiz. (2014). Cholesterol-Induced Impact on Murine Macrophage Responsiveness Involves down-Regulation of Mevalonate Pathway. Advances in Biochemistry, 2(1), 24-28. https://doi.org/10.11648/j.ab.20140201.14

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ACS Style

Yakov Sh. Schwartz; Olga M. Dolganova; Sergey V. Cheresiz. Cholesterol-Induced Impact on Murine Macrophage Responsiveness Involves down-Regulation of Mevalonate Pathway. Adv. Biochem. 2014, 2(1), 24-28. doi: 10.11648/j.ab.20140201.14

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AMA Style

Yakov Sh. Schwartz, Olga M. Dolganova, Sergey V. Cheresiz. Cholesterol-Induced Impact on Murine Macrophage Responsiveness Involves down-Regulation of Mevalonate Pathway. Adv Biochem. 2014;2(1):24-28. doi: 10.11648/j.ab.20140201.14

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@article{10.11648/j.ab.20140201.14,
  author = {Yakov Sh. Schwartz and Olga M. Dolganova and Sergey V. Cheresiz},
  title = {Cholesterol-Induced Impact on Murine Macrophage Responsiveness Involves down-Regulation of Mevalonate Pathway},
  journal = {Advances in Biochemistry},
  volume = {2},
  number = {1},
  pages = {24-28},
  doi = {10.11648/j.ab.20140201.14},
  url = {https://doi.org/10.11648/j.ab.20140201.14},
  eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.ab.20140201.14},
  abstract = {Free cholesterol (Ch) and its oxidative derivatives, oxysterols, are often accumulated in macrophages during chronic inflammation and atherogenesis. The effects of Ch and oxysterols on the balance of pro- and anti-inflammatory cytokines in inflammatory response and the role of mevalonate pathway in the effects of these sterols are studied poorly. We studied the effects of cholesterol, oxysterols, atorvastatin, and mevalonic acid on the LPS-induced TNF-α, IL-10, and TGF-β1 production in macrophage cell culture. The study was carried out in murine peritoneal macrophages preincubated for 4 h with Ch (5 µg/mL), 25-hydroxycholesterol (25-OH-Ch) (5 µg/mL), 7-keto-Ch (5 µg/mL), farnesol (10 µM), or atorvastatin (5 µmol/mL) in the presence or absence of 1 mM of mevalonate. The cells were further incubated in the presence or absence of E. coli 0111:B4 lipopolysaccharide (LPS) for 24 h, and cytokine concentrations in incubation media were determined. Macrophages preincubation with Ch, 25-OH-Ch, or atorvastatin decreased LPS-induced TNF-α production in cell cultures, while supplementation of preincubation medium with mevalonic acid abrogated the effects of atorvastatin and Ch. The Ch, 25-OH-Ch, 7-keto-Ch and atorvastatin significantly reduced IL-10 production by LPS–stimulated macrophages, while farnesol had no effect. Supplementation of Ch or atorvastatin-containing preincubation medium with mevalonate restored IL-10 production. The TGF-β1 production was significantly enhanced by the presence of Ch or atorvastatin in preincubation medium as compared to the control level in non-treated macrophages, while 25-OH-Ch or farnesol decreased profoundly TGF-β1 production. Mevalonate abrogated the effect of Ch or atorvastatin but not of 25-OH-Ch or farnesol. These results allow to conclude, that Ch is able to promote anti-inflammatory and fibrogenic macrophage response, which is connected, at least in part, with the deficiency of mevalonate pathway intermediates, particularly to the deficiency of farnesol, whereas hydroxysterols produce tolerogenic, but not fibrogenic effect, independently of mevalonate pathway.},
 year = {2014}
}

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TY  - JOUR
T1  - Cholesterol-Induced Impact on Murine Macrophage Responsiveness Involves down-Regulation of Mevalonate Pathway
AU  - Yakov Sh. Schwartz
AU  - Olga M. Dolganova
AU  - Sergey V. Cheresiz
Y1  - 2014/03/10
PY  - 2014
N1  - https://doi.org/10.11648/j.ab.20140201.14
DO  - 10.11648/j.ab.20140201.14
T2  - Advances in Biochemistry
JF  - Advances in Biochemistry
JO  - Advances in Biochemistry
SP  - 24
EP  - 28
PB  - Science Publishing Group
SN  - 2329-0862
UR  - https://doi.org/10.11648/j.ab.20140201.14
AB  - Free cholesterol (Ch) and its oxidative derivatives, oxysterols, are often accumulated in macrophages during chronic inflammation and atherogenesis. The effects of Ch and oxysterols on the balance of pro- and anti-inflammatory cytokines in inflammatory response and the role of mevalonate pathway in the effects of these sterols are studied poorly. We studied the effects of cholesterol, oxysterols, atorvastatin, and mevalonic acid on the LPS-induced TNF-α, IL-10, and TGF-β1 production in macrophage cell culture. The study was carried out in murine peritoneal macrophages preincubated for 4 h with Ch (5 µg/mL), 25-hydroxycholesterol (25-OH-Ch) (5 µg/mL), 7-keto-Ch (5 µg/mL), farnesol (10 µM), or atorvastatin (5 µmol/mL) in the presence or absence of 1 mM of mevalonate. The cells were further incubated in the presence or absence of E. coli 0111:B4 lipopolysaccharide (LPS) for 24 h, and cytokine concentrations in incubation media were determined. Macrophages preincubation with Ch, 25-OH-Ch, or atorvastatin decreased LPS-induced TNF-α production in cell cultures, while supplementation of preincubation medium with mevalonic acid abrogated the effects of atorvastatin and Ch. The Ch, 25-OH-Ch, 7-keto-Ch and atorvastatin significantly reduced IL-10 production by LPS–stimulated macrophages, while farnesol had no effect. Supplementation of Ch or atorvastatin-containing preincubation medium with mevalonate restored IL-10 production. The TGF-β1 production was significantly enhanced by the presence of Ch or atorvastatin in preincubation medium as compared to the control level in non-treated macrophages, while 25-OH-Ch or farnesol decreased profoundly TGF-β1 production. Mevalonate abrogated the effect of Ch or atorvastatin but not of 25-OH-Ch or farnesol. These results allow to conclude, that Ch is able to promote anti-inflammatory and fibrogenic macrophage response, which is connected, at least in part, with the deficiency of mevalonate pathway intermediates, particularly to the deficiency of farnesol, whereas hydroxysterols produce tolerogenic, but not fibrogenic effect, independently of mevalonate pathway.
VL  - 2
IS  - 1
ER  -

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Author Information

Yakov Sh. Schwartz

FSBI ?Research Institute of Internal and Preventive Medicine?, SB RAS, Novosibirsk, Russia
Olga M. Dolganova

FSBI ?Research Institute of Internal and Preventive Medicine?, SB RAS, Novosibirsk, Russia
Sergey V. Cheresiz

FSBI ?Research Institute of Internal and Preventive Medicine?, SB RAS, Novosibirsk, Russia

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APA Style

Yakov Sh. Schwartz, Olga M. Dolganova, Sergey V. Cheresiz. (2014). Cholesterol-Induced Impact on Murine Macrophage Responsiveness Involves down-Regulation of Mevalonate Pathway. Advances in Biochemistry, 2(1), 24-28. https://doi.org/10.11648/j.ab.20140201.14

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ACS Style

Yakov Sh. Schwartz; Olga M. Dolganova; Sergey V. Cheresiz. Cholesterol-Induced Impact on Murine Macrophage Responsiveness Involves down-Regulation of Mevalonate Pathway. Adv. Biochem. 2014, 2(1), 24-28. doi: 10.11648/j.ab.20140201.14

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AMA Style

Yakov Sh. Schwartz, Olga M. Dolganova, Sergey V. Cheresiz. Cholesterol-Induced Impact on Murine Macrophage Responsiveness Involves down-Regulation of Mevalonate Pathway. Adv Biochem. 2014;2(1):24-28. doi: 10.11648/j.ab.20140201.14

Copy | Download

@article{10.11648/j.ab.20140201.14,
  author = {Yakov Sh. Schwartz and Olga M. Dolganova and Sergey V. Cheresiz},
  title = {Cholesterol-Induced Impact on Murine Macrophage Responsiveness Involves down-Regulation of Mevalonate Pathway},
  journal = {Advances in Biochemistry},
  volume = {2},
  number = {1},
  pages = {24-28},
  doi = {10.11648/j.ab.20140201.14},
  url = {https://doi.org/10.11648/j.ab.20140201.14},
  eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.ab.20140201.14},
  abstract = {Free cholesterol (Ch) and its oxidative derivatives, oxysterols, are often accumulated in macrophages during chronic inflammation and atherogenesis. The effects of Ch and oxysterols on the balance of pro- and anti-inflammatory cytokines in inflammatory response and the role of mevalonate pathway in the effects of these sterols are studied poorly. We studied the effects of cholesterol, oxysterols, atorvastatin, and mevalonic acid on the LPS-induced TNF-α, IL-10, and TGF-β1 production in macrophage cell culture. The study was carried out in murine peritoneal macrophages preincubated for 4 h with Ch (5 µg/mL), 25-hydroxycholesterol (25-OH-Ch) (5 µg/mL), 7-keto-Ch (5 µg/mL), farnesol (10 µM), or atorvastatin (5 µmol/mL) in the presence or absence of 1 mM of mevalonate. The cells were further incubated in the presence or absence of E. coli 0111:B4 lipopolysaccharide (LPS) for 24 h, and cytokine concentrations in incubation media were determined. Macrophages preincubation with Ch, 25-OH-Ch, or atorvastatin decreased LPS-induced TNF-α production in cell cultures, while supplementation of preincubation medium with mevalonic acid abrogated the effects of atorvastatin and Ch. The Ch, 25-OH-Ch, 7-keto-Ch and atorvastatin significantly reduced IL-10 production by LPS–stimulated macrophages, while farnesol had no effect. Supplementation of Ch or atorvastatin-containing preincubation medium with mevalonate restored IL-10 production. The TGF-β1 production was significantly enhanced by the presence of Ch or atorvastatin in preincubation medium as compared to the control level in non-treated macrophages, while 25-OH-Ch or farnesol decreased profoundly TGF-β1 production. Mevalonate abrogated the effect of Ch or atorvastatin but not of 25-OH-Ch or farnesol. These results allow to conclude, that Ch is able to promote anti-inflammatory and fibrogenic macrophage response, which is connected, at least in part, with the deficiency of mevalonate pathway intermediates, particularly to the deficiency of farnesol, whereas hydroxysterols produce tolerogenic, but not fibrogenic effect, independently of mevalonate pathway.},
 year = {2014}
}

Copy | Download

TY  - JOUR
T1  - Cholesterol-Induced Impact on Murine Macrophage Responsiveness Involves down-Regulation of Mevalonate Pathway
AU  - Yakov Sh. Schwartz
AU  - Olga M. Dolganova
AU  - Sergey V. Cheresiz
Y1  - 2014/03/10
PY  - 2014
N1  - https://doi.org/10.11648/j.ab.20140201.14
DO  - 10.11648/j.ab.20140201.14
T2  - Advances in Biochemistry
JF  - Advances in Biochemistry
JO  - Advances in Biochemistry
SP  - 24
EP  - 28
PB  - Science Publishing Group
SN  - 2329-0862
UR  - https://doi.org/10.11648/j.ab.20140201.14
AB  - Free cholesterol (Ch) and its oxidative derivatives, oxysterols, are often accumulated in macrophages during chronic inflammation and atherogenesis. The effects of Ch and oxysterols on the balance of pro- and anti-inflammatory cytokines in inflammatory response and the role of mevalonate pathway in the effects of these sterols are studied poorly. We studied the effects of cholesterol, oxysterols, atorvastatin, and mevalonic acid on the LPS-induced TNF-α, IL-10, and TGF-β1 production in macrophage cell culture. The study was carried out in murine peritoneal macrophages preincubated for 4 h with Ch (5 µg/mL), 25-hydroxycholesterol (25-OH-Ch) (5 µg/mL), 7-keto-Ch (5 µg/mL), farnesol (10 µM), or atorvastatin (5 µmol/mL) in the presence or absence of 1 mM of mevalonate. The cells were further incubated in the presence or absence of E. coli 0111:B4 lipopolysaccharide (LPS) for 24 h, and cytokine concentrations in incubation media were determined. Macrophages preincubation with Ch, 25-OH-Ch, or atorvastatin decreased LPS-induced TNF-α production in cell cultures, while supplementation of preincubation medium with mevalonic acid abrogated the effects of atorvastatin and Ch. The Ch, 25-OH-Ch, 7-keto-Ch and atorvastatin significantly reduced IL-10 production by LPS–stimulated macrophages, while farnesol had no effect. Supplementation of Ch or atorvastatin-containing preincubation medium with mevalonate restored IL-10 production. The TGF-β1 production was significantly enhanced by the presence of Ch or atorvastatin in preincubation medium as compared to the control level in non-treated macrophages, while 25-OH-Ch or farnesol decreased profoundly TGF-β1 production. Mevalonate abrogated the effect of Ch or atorvastatin but not of 25-OH-Ch or farnesol. These results allow to conclude, that Ch is able to promote anti-inflammatory and fibrogenic macrophage response, which is connected, at least in part, with the deficiency of mevalonate pathway intermediates, particularly to the deficiency of farnesol, whereas hydroxysterols produce tolerogenic, but not fibrogenic effect, independently of mevalonate pathway.
VL  - 2
IS  - 1
ER  -

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