Dual knockdown of p65 and p50 subunits of NF-kappaB by siRNA inhibits the induction of inflammatory cytokines and significantly enhance apoptosis in human primary synoviocytes treated with tumor necrosis factor-alpha

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Title
Dual knockdown of p65 and p50 subunits of NF-kappaB by siRNA inhibits the induction of inflammatory cytokines and significantly enhance apoptosis in human primary synoviocytes treated with tumor necrosis factor-alpha
Author(s)
U J Lee; S R Choung; K V B Prakash; E J Lee; M Y Lee; Young Joo Kim; C W Han; Y C Choi
Bibliographic Citation
Molecular Biology Reports, vol. 35, no. 3, pp. 291-298
Publication Year
2008
Abstract
In order to develop an anti-NF-κB siRNA as a novel class of anti-inflammatory drug, we have isolated a highly efficient siRNA targeting the p65 (RelA) subunit of NF-κB, hereafter named REL1096. To determine whether down-regulation of p65 by REL1096 can block the induction of inflammatory cytokines after treatment with tumor necrosis factor-alpha (TNF-α), human primary fibroblast-like synoviocytes were isolated from patients with rheumatoid arthritis. When treated with REL1096, the TNF-mediated induction of downstream target genes such as inflammatory cytokines, chemokines, and anti-apoptosis genes was drastically inhibited. To enhance the inhibitory effect of REL1096, cells were treated with siRNA targeting the p50 subunit of NF-κB together with REL1096. In addition to effective downregulation of inflammatory cytokines, knockdown of both p65 and p50 resulted in much more extensive apoptosis when compared to cells treated with either REL1096 or p50-siRNA alone. Thus, our results provide evidence for the potential use of siRNA targeting NF-κB as an effective means to treat rheumatoid arthritis. In addition to effective amelioration of synovial inflammation by downregulation of inflammatory cytokines, increased apoptosis by dual knockdown of p65 and p50 may prove advantageous in preventing invasiveness and destructiveness of hyperplastic synoviocytes.
Keyword
Rheumatoid arthritisp50siRNAApoptosisFibroblast-like synoviocyteNF-κB p65
ISSN
0301-4851
Publisher
Springer
DOI
http://dx.doi.org/10.1007/s11033-007-9084-4
Type
Article
Appears in Collections:
1. Journal Articles > Journal Articles
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