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PCSK9 siRNA suppresses the inflammatory response induced by oxLDL through inhibition of NF-κB activation in THP-1-derived macrophages
- Source :
- International journal of molecular medicine. 30(4)
- Publication Year :
- 2012
-
Abstract
- Proprotein convertase subtilisin/kexin 9 (PCSK9), a member of the protein-converting enzyme family, is highly expressed in adult hepatocytes and small intestinal enterocytes. To our knowledge, in this study, we demonstrate for the first time that PCSK9 is upregulated in a dose-dependent manner via oxidized low-density lipoprotein (oxLDL) stimulation in THP-1-derived macrophages. PCSK9 small interfering RNA (siRNA) suppresses the oxLDL-induced inflammatory cytokine expression in THP-1-derived macrophages. The exposure of macrophages to oxLDL markedly increased the expression of NF-κB protein in the nucleus. However, this effect was significantly attenuated by PCSK9 siRNA. These findings indicate that PCSK9 expression is induced by oxLDL, and that PCSK9 siRNA protects against inflammation via the inhibition of NF-κB activation in oxLDL-stimulated THP-1-derived macrophages. Our results suggest that PCSK9 may be used as a therapeutic target for the treatment of atherosclerosis since PCSK9 siRNA suppresses oxLDL-induced IκB-α degradation and NF-κB nuclear translocation into THP-1-derived macrophages.
- Subjects :
- Small interfering RNA
Inflammation
Biology
Cell Line
Downregulation and upregulation
Genetics
medicine
Humans
THP1 cell line
RNA, Small Interfering
Oncogene
Macrophages
Serine Endopeptidases
NF-kappa B
General Medicine
Proprotein convertase
Molecular biology
Up-Regulation
Lipoproteins, LDL
Apoptosis
Kexin
lipids (amino acids, peptides, and proteins)
RNA Interference
Proprotein Convertases
medicine.symptom
Proprotein Convertase 9
Subjects
Details
- ISSN :
- 1791244X
- Volume :
- 30
- Issue :
- 4
- Database :
- OpenAIRE
- Journal :
- International journal of molecular medicine
- Accession number :
- edsair.doi.dedup.....329554bca18c62d346b7f8afedfb44bf