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The interleukin-33-mediated inhibition of expression of two key genes implicated in atherosclerosis in human macrophages requires MAP kinase, phosphoinositide 3-kinase and nuclear factor-κB signaling pathways
- Source :
- Scientific Reports, Vol 9, Iss 1, Pp 1-12 (2019), Scientific Reports
- Publication Year :
- 2019
- Publisher :
- Nature Publishing Group, 2019.
-
Abstract
- Atherosclerosis, a chronic inflammatory disorder of the walls of arteries, causes more deaths worldwide than any other disease. Cytokines, which are present at high levels in atherosclerotic plaques, play important roles in regulating the initiation and the progression of the disease. Previous studies using animal and cell culture model systems revealed protective, anti-atherogenic effects of the cytokine interleukin-33 (IL-33). The action of this cytokine involves both the induction and suppression of expression of many genes. Unfortunately, the signaling pathways that are responsible for the inhibition of gene expression by this cytokine are poorly understood. Further studies are required given the important roles of genes whose expression is inhibited by IL-33 in key cellular processes associated with atherosclerosis such as monocyte recruitment, foam cell formation and lipoprotein metabolism. We have investigated here the roles of various known IL-33 activated signaling pathways in such inhibitory actions using RNA interference-mediated knockdown assays and monocyte chemotactic protein-1 and intercellular adhesion molecule-1 as model genes. Key roles were identified for extracellular signal-regulated kinase-1/2, p38α kinase, c-Jun N-terminal kinase-1/2, phosphoinositide 3-kinase-γ, and p50 and p65 nuclear factor-κB in such inhibitory action of IL-33. These studies provide new insights on the signaling pathways through which IL-33 inhibits the macrophage expression of key atherosclerosis-associated genes.
- Subjects :
- 0301 basic medicine
medicine.medical_treatment
Down-Regulation
lcsh:Medicine
Biology
Article
03 medical and health sciences
0302 clinical medicine
medicine
Humans
lcsh:Science
Chemokine CCL2
Foam cell
Gene knockdown
Multidisciplinary
Phosphoinositide 3-kinase
Molecular medicine
Kinase
Macrophages
Interleukins
Monocyte
lcsh:R
NF-kappa B
Atherosclerosis
Intercellular Adhesion Molecule-1
Interleukin-33
Cell biology
Interleukin 33
030104 developmental biology
Cytokine
medicine.anatomical_structure
Gene Expression Regulation
biology.protein
lcsh:Q
Mitogen-Activated Protein Kinases
Phosphatidylinositol 3-Kinase
Signal transduction
030217 neurology & neurosurgery
Signal Transduction
Subjects
Details
- Language :
- English
- ISSN :
- 20452322
- Database :
- OpenAIRE
- Journal :
- Scientific Reports, Vol 9, Iss 1, Pp 1-12 (2019), Scientific Reports
- Accession number :
- edsair.doi.dedup.....0cb16dd3ea8ea9f2e07f0faf39be5f1b