Journal article
Locally instilled tumor necrosis factor a antisense oligonucleotide contributes to inhibition of T(H)2-driven pulmonary fibrosis via induced CD4(+)CD25(+)Foxp3(+) regulatory T cells
The journal of gene medicine, Vol.15(11-12), pp.441-452
11/01/2013
DOI: 10.1002/jgm.2750
PMID: 24339053
Abstract
BackgroundAnti-tumor necrosis factor therapeutics has the potential to alleviate pulmonary fibrosis. However, the systemic administration of anti-tumor necrosis factor agents has brought about contradictory results and frequent adverse effects, such as infections, immunogenicity and malignancies, amongst others. In the present study, we attempted the local administration of tumor necrosis factor antisense oligonucleotide and evaluated the treatment effects on pulmonary fibrosis in a bleomycin-induced pulmonary fibrosis mouse model.
MethodsFlow cytometry for regulatory T cells, reverse transcriptase-polymerase chain reaction for crucial gene expression, western blotting for crucial protein products, immunofluorescent analysis for T(H)2 cells and myofibroblasts, as well as histology analysis for pathological examination, were used.
ResultsBy local administration of tumor necrosis factor antisense oligonucleotide, we investigated whether tumor necrosis factor expression in epithelial cells was significantly inhibited and extracellular matrix overexpression was dramatically reduced. These treatment effects were associated with induced regulatory T cells, reduced T(H)2 cells and generally decreased T(H)2-type cytokine expression. Systemic immunosuppression was not triggered by local antisense oligonucleotide administration because the proportion of regulatory T cells in the blood, thymus or spleen was not affected.
ConclusionsThese findings demonstrate that local administration of tumor necrosis factor antisense oligonucleotide contributes to anti-fibrotic action via a sustained up-regulated level of regulatory T cells, which inhibits T(H)2-biased responses, pro-fibrotic mediator production and extracellular matrix deposition, with no systemic immunosupression associated with systemically induced regulatory T cells. Copyright (c) 2013 John Wiley & Sons, Ltd.
Details
- Title: Subtitle
- Locally instilled tumor necrosis factor a antisense oligonucleotide contributes to inhibition of T(H)2-driven pulmonary fibrosis via induced CD4(+)CD25(+)Foxp3(+) regulatory T cells
- Creators
- Yi Luo - Nanjing UniversityMin Wang - Nanjing UniversityZhonghua Pang - Nanjing UniversityFengtao Jiang - Nanjing UniversityJiangning Chen - Nanjing UniversityJunfeng Zhang - Nanjing University
- Resource Type
- Journal article
- Publication Details
- The journal of gene medicine, Vol.15(11-12), pp.441-452
- Publisher
- Wiley
- DOI
- 10.1002/jgm.2750
- PMID
- 24339053
- ISSN
- 1099-498X
- eISSN
- 1521-2254
- Number of pages
- 12
- Grant note
- J1103512 / NSFC; National Natural Science Foundation of China (NSFC) BK 2009237 / Jiangsu Provincial Natural Science Foundation of China; Natural Science Foundation of Jiangsu Province 2012CB517603 / National Basic Research Program of China Fundamental Research Funds for the Central Universities 108059 / Key Project of the Chinese Ministry of Education; Ministry of Education, China 31070722; 31271013; 31071232; 31170751; 31200695; 51173076; 91129712; 81102489 / National Natural Science Foundation of China; National Natural Science Foundation of China (NSFC) 81025019 / National Science Fund for Distinguished Young Scholars; National Natural Science Foundation of China (NSFC) 20100091120020 / PhD Programs Foundation of the Ministry of Education of China; Ministry of Education, China
- Language
- English
- Date published
- 11/01/2013
- Academic Unit
- Urology
- Record Identifier
- 9984319979202771
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