Format

Send to

Choose Destination
See comment in PubMed Commons below
Biochem Biophys Res Commun. 2009 Jan 2;378(1):90-4. doi: 10.1016/j.bbrc.2008.11.002. Epub 2008 Nov 11.

Inhibition of IL-1beta-mediated inflammatory responses by the IkappaB alpha super-repressor in human fibroblast-like synoviocytes.

Author information

1
Department of Biochemistry, Medical School and Diabetes Research Center, Chonbuk National University, Jeonju, Jeonbuk 561-756, Republic of Korea.

Abstract

The IL-1beta-NF-kappaB axis is a key pathway in the pathogenesis of rheumatoid arthritis (RA) and is central in the production of proinflammatory mediators in the inflamed synovium. Therefore, we examined whether fibroblast-like synoviocytes (FLS) could be spared from IL-1beta-induced toxicity by an overexpressing IkappaB super-repressor. Infection of FLS with Ad-IkappaB alpha (S32A, S36A), an adenovirus-containing mutant IkappaB alpha, inhibited IL-1beta-induced nuclear translocation and DNA binding of NF-kappaB. In addition, Ad-IkappaB alpha (S32A, S36A) prevented IL-1beta-induced inflammatory responses; namely, the production of chemokines, such as ENA-78 and RANTES, and activation of MMP-1 and MMP-3. Finally, increased cellular proliferation of FLS after IL-1beta treatment was significantly reduced by Ad-IkappaB alpha (S32A, S36A). However, Ad-IkappaB beta (S19A, S23A), the IkappaB beta mutant, was not effective in preventing IL-1beta toxicity. These results suggest that inhibition of IkappaB alpha degradation is a potential target for the prevention of joint destruction in patients with RA.

PMID:
19007749
DOI:
10.1016/j.bbrc.2008.11.002
[Indexed for MEDLINE]
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science
    Loading ...
    Support Center