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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.

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


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.

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