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Cholesterol: Significance and Regulation01:29

Cholesterol: Significance and Regulation

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Although not a source of energy, cholesterol plays a significant role as a foundational structure for bile salts, steroid hormones, and vitamin D, as well as being a crucial component of plasma membranes. Approximately 15% of blood cholesterol is derived from our diet, with the remainder synthesized from acetyl CoA by the liver and intestines. Cholesterol is eliminated from the body through its conversion into bile salts, which are eventually discarded in the feces.
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Differentiation of Functional Osteoclasts from Human Peripheral Blood CD14+ Monocytes
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Atheroma-Relevant 7-Oxysterols Differentially Upregulate Cd14 Expression.

Bo-Young Kim1, Yonghae Son1, Byoung Joon Kim2,3

  • 1Department of Pharmacology, School of Medicine, Pusan National University, Yangsan 50612, Republic of Korea.

International Journal of Molecular Sciences
|July 14, 2023
PubMed
Summary
This summary is machine-generated.

Atherosclerotic lesions show increased CD14 expression, linked to 7-oxysterols. These compounds, particularly 7α-hydroxycholesterol, upregulate CD14 in monocytic cells, influencing inflammation and cell migration.

Keywords:
7-oxysterolsCD14MMP-9THP-1 cellsinflammation

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Area of Science:

  • Biochemistry
  • Immunology
  • Cell Biology

Background:

  • CD14 expression is elevated in atherosclerotic lesions, sites rich in 7-oxysterols.
  • The precise role of 7-oxysterols in regulating CD14 expression in vascular cells remains unclear.

Purpose of the Study:

  • To investigate the effects of specific 7-oxysterols (7α-hydroxycholesterol, 7β-hydroxycholesterol, 7-ketocholesterol) on CD14 expression in THP-1 monocytic cells.
  • To elucidate the mechanisms by which 7-oxysterols modulate CD14 levels and related cellular functions.

Main Methods:

  • THP-1 cells were treated with different 7-oxysterols.
  • CD14 transcript and protein levels were quantified.
  • Soluble CD14 (sCD14) release and monocytic cell responses to lipopolysaccharides were assessed.
  • Matrix metalloproteinase-9 (MMP-9) activity was measured, and the effect of an MMP-9 inhibitor on sCD14 release was evaluated.

Main Results:

  • All three tested 7-oxysterols increased CD14 transcript and protein levels and promoted sCD14 release from THP-1 cells.
  • 7α-hydroxycholesterol demonstrated the strongest induction of CD14 expression.
  • 7α-hydroxycholesterol upregulated membrane-bound CD14, enhancing lipopolysaccharide-induced CCL2 production and monocytic cell migration.
  • 7-oxysterols increased MMP-9 activity, and inhibiting MMP-9 significantly reduced sCD14 release.

Conclusions:

  • 7-oxysterols differentially induce CD14 expression in vascular cells.
  • These findings suggest that 7-oxysterols contribute to monocytic CD14 expression through distinct, yet overlapping, mechanisms involving MMP-9.
  • The study highlights a potential link between oxysterol metabolism and inflammatory processes in atherosclerosis.