title: Molecular mechanisms of PDGF-AA expression induced by the dsRNA-mimetic poly (I:C) and IL-18.
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.
authors.affiliation: Pharmacology and Toxicology Department, Faculty of Pharmacy, Al-Azhar University, Cairo, Egypt.
authors.forename: Amany
authors.initials: A
authors.lastname: Balah
authors.forename: Heiko
authors.initials: H
authors.lastname: Mühl
authors.forename: Josef
authors.initials: J
authors.lastname: Pfeilschifter
authors.forename: El-Sayed
authors.initials: el-S
authors.lastname: Akool
mesh_terms: D002460:Cell Line; D003713:Dendritic Cells / Q000187:drug effects* / Q000378:metabolism*; D006801:Humans; D020382:Interleukin-18 / Q000494:pharmacology*; D010982:Platelet-Derived Growth Factor / Q000378:metabolism*; D011070:Poly I-C / Q000737:chemistry / Q000494:pharmacology*; D012330:RNA, Double-Stranded / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D020382:Interleukin-18; D010982:Platelet-Derived Growth Factor; D012330:RNA, Double-Stranded; C075278:platelet-derived growth factor A; D011070:Poly I-C