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Mol Med Rep. 2014 Mar;9(3):899-903. doi: 10.3892/mmr.2014.1893. Epub 2014 Jan 13.

Local delivery of T-bet shRNA reduces inflammation in collagen II-induced arthritis via downregulation of IFN-γ and IL-17.

Author information

1
Department of Immunology, Institute of Laboratory Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, P.R. China.
2
The Affiliated People's Hospital of Jiangsu University, Zhenjiang, Jiangsu 212001, P.R. China.

Abstract

Th1 and Th17 cells are involved in the pathogenesis of rheumatoid arthritis (RA). T-bet, a Th1-specific transcription factor, appears to drive the maturation of Th1 and IFN-γ secretion. In the present study, we established the T-bet shRNA recombinant plasmid (p-T-shRNA) and explored its possible anti-inflammatory effect in a collagen-induced arthritis (CIA) model by local injection of plasmid vectors. For the initiation of CIA, DBA/1J mice were immunized with type II collagen (CII) in Freund's adjuvant and the CII-immunized mice were treated with p-T-shRNA. Levels of T-bet, IFN-γ, IL-17 and RORγt mRNA in splenocytes and synovial joints were measured by quantitative real-time PCR and T-bet expression in joint tissue was detected by immunohistochemistry staining. The intracellular IFN-γ and IL-17 were analyzed by flow cytometry (FCM). The results demonstrated that therapeutic administration on the local joints with p-T-shRNA significantly suppressed IFN-γ and IL-17 gene expression and improved the pathogenesis of arthritis in CIA mice, while administration of a plasmid expressing T-bet (pIRES-T-bet) accelerated the disease onset. Our study suggests that T-bet may be developed as a potential target for arthritis therapy.

PMID:
24425064
DOI:
10.3892/mmr.2014.1893
[Indexed for MEDLINE]
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