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Molecular mechanisms of PDGF-AA expression induced by the dsRNA-mimetic poly (I:C) and IL-18
- Source :
- Biochemical and Biophysical Research Communications. 435:691-695
- Publication Year :
- 2013
- Publisher :
- Elsevier BV, 2013.
-
Abstract
- Several animal studies suggest a role of platelet-derived growth factors (PDGFs) particularly A and B in atherosclerosis. Previously, it has been shown that viral infections have the ability to initiate and accelerate atherosclerosis in animal models. Recently, it has been reported that IL-18 has a pro-atherogenic character. Moreover, viral infections have been shown to be associated with induction of IL-18 bioactivity. By using human predendritic KG1 cells, we sought to assess PDGF-AA production under the influence of IL-18 and the byproduct of viral replication, dsRNA-mimetic poly (I:C). Here we demonstrate that poly (I:C) and IL-18 have the ability to induce PDGF-AA expression. In addition, costimulation of KG-1 cells with both IL-18 plus poly (I:C) shows an additive effect on PDGF-AA production. Furthermore, we demonstrate that neither p38 nor SAPK/JNK is required for PDGF-AA production by both PIC and IL-18. However, the expression of PDGF-AA has been found to be associated with increased activation of NF-κB and enhancement of DNA-binding capacity of NF-κB as shown by electrophoretic mobility shift assay (EMSA) and supershift analysis. Collectively, this study demonstrates that the byproduct of viral replication, dsRNA [poly (I:C)], and IL-18 have the ability to induce PDGF-AA in NF-κB-dependent manner. Furthermore, dsRNA act in an additive way with IL-18 to induce PDGF-AA which plays a major role in atherosclerosis. These data might help to understand the pro-atherogenic character of IL-18 and molecular mechanisms of viral infection-induced atherosclerosis.
- Subjects :
- Platelet-Derived Growth Factor
p38 mitogen-activated protein kinases
Interleukin-18
Biophysics
RNA
Dendritic Cells
Cell Biology
Biology
Biochemistry
Virology
Cell Line
Cell biology
RNA silencing
Poly I-C
Viral replication
Cell culture
biology.protein
Humans
Electrophoretic mobility shift assay
Animal studies
Molecular Biology
Platelet-derived growth factor receptor
RNA, Double-Stranded
Subjects
Details
- ISSN :
- 0006291X
- Volume :
- 435
- Database :
- OpenAIRE
- Journal :
- Biochemical and Biophysical Research Communications
- Accession number :
- edsair.doi.dedup.....abdc306039f9a482fb99d587e6fdeb32