siRNA-mediated c-Rel knockdown ameliorates collagen-induced arthritis in mice

siRNA-mediated c-Rel knockdown ameliorates collagen-induced arthritis in mice Previous studies have shown that inflammatory mediators involved in the development of rheumatoid arthritis (RA) are regulated by the Rel/nuclear factor-κB (Rel/NF-κB) transcription factor family. c-Rel, a member of the Rel/NF-κB family that is preferentially expressed by immune cells, is a risk factor for several inflammatory diseases including RA. In the current study, we investigated whether targeting c-Rel can be used to treat collagen-induced arthritis, an animal model for RA. c-Rel specific siRNA (siRel) delivered by nanoparticles was used to knockdown the expression of c-Rel. Our results showed that siRel treatment significantly ameliorated collagen-induced arthritis. Further study revealed that c-Rel expression in the dendritic cells and macrophages from mice treated with siRel was significantly down-regulated. Consistent with the phenotypical result, the expression of inflammatory cytokines TNF-α, IL-1β, IL-6, IL-12 and IL-23 by peritoneal macrophages and splenocytes were significantly decreased. In addition, attenuated systemic and collagen-specific Th1 and Th17 immune responses were observed. Furthermore, we found that the expression of inflammatory cytokines was significantly down-regulated and the infiltration of CD3+ T cells and F4/80+ macrophages was markedly reduced in hind paws of mice treated with siRel. Collectively, our study provides strong evidence that siRNA-mediated c-Rel knockdown can suppress the development of collagen-induced arthritis in mice. Therefore, blocking c-Rel may represent an attracting strategy for the treatment of human rheumatoid arthritis. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png International Immunopharmacology Elsevier

siRNA-mediated c-Rel knockdown ameliorates collagen-induced arthritis in mice

Loading next page...
 
/lp/elsevier/sirna-mediated-c-rel-knockdown-ameliorates-collagen-induced-arthritis-5Ya59sWCok
Publisher
Elsevier
Copyright
Copyright © 2018 Elsevier B.V.
ISSN
1567-5769
eISSN
1878-1705
D.O.I.
10.1016/j.intimp.2018.01.010
Publisher site
See Article on Publisher Site

Abstract

Previous studies have shown that inflammatory mediators involved in the development of rheumatoid arthritis (RA) are regulated by the Rel/nuclear factor-κB (Rel/NF-κB) transcription factor family. c-Rel, a member of the Rel/NF-κB family that is preferentially expressed by immune cells, is a risk factor for several inflammatory diseases including RA. In the current study, we investigated whether targeting c-Rel can be used to treat collagen-induced arthritis, an animal model for RA. c-Rel specific siRNA (siRel) delivered by nanoparticles was used to knockdown the expression of c-Rel. Our results showed that siRel treatment significantly ameliorated collagen-induced arthritis. Further study revealed that c-Rel expression in the dendritic cells and macrophages from mice treated with siRel was significantly down-regulated. Consistent with the phenotypical result, the expression of inflammatory cytokines TNF-α, IL-1β, IL-6, IL-12 and IL-23 by peritoneal macrophages and splenocytes were significantly decreased. In addition, attenuated systemic and collagen-specific Th1 and Th17 immune responses were observed. Furthermore, we found that the expression of inflammatory cytokines was significantly down-regulated and the infiltration of CD3+ T cells and F4/80+ macrophages was markedly reduced in hind paws of mice treated with siRel. Collectively, our study provides strong evidence that siRNA-mediated c-Rel knockdown can suppress the development of collagen-induced arthritis in mice. Therefore, blocking c-Rel may represent an attracting strategy for the treatment of human rheumatoid arthritis.

Journal

International ImmunopharmacologyElsevier

Published: Mar 1, 2018

References

You’re reading a free preview. Subscribe to read the entire article.


DeepDyve is your
personal research library

It’s your single place to instantly
discover and read the research
that matters to you.

Enjoy affordable access to
over 18 million articles from more than
15,000 peer-reviewed journals.

All for just $49/month

Explore the DeepDyve Library

Search

Query the DeepDyve database, plus search all of PubMed and Google Scholar seamlessly

Organize

Save any article or search result from DeepDyve, PubMed, and Google Scholar... all in one place.

Access

Get unlimited, online access to over 18 million full-text articles from more than 15,000 scientific journals.

Your journals are on DeepDyve

Read from thousands of the leading scholarly journals from SpringerNature, Elsevier, Wiley-Blackwell, Oxford University Press and more.

All the latest content is available, no embargo periods.

See the journals in your area

DeepDyve

Freelancer

DeepDyve

Pro

Price

FREE

$49/month
$360/year

Save searches from
Google Scholar,
PubMed

Create lists to
organize your research

Export lists, citations

Read DeepDyve articles

Abstract access only

Unlimited access to over
18 million full-text articles

Print

20 pages / month

PDF Discount

20% off