Journal article
Locally instilled tumor necrosis factor-alpha antisense oligonucleotide inhibits allergic inflammation via the induction of Tregs
The journal of gene medicine, Vol.14(6), pp.374-383
06/01/2012
DOI: 10.1002/jgm.2631
PMID: 22576979
Abstract
Background Anti-tumor necrosis factor (TNF)-a therapeutics has the potential to alleviate allergic inflammation. However, in previous studies, the systemic administration of anti-TNF-a agents was frequently accompanied by many adverse effects, such as infection, immunogenicity and malignancy. Efforts are made in the present study to evaluate whether or not local administration of TNF-a antisense oligonucleotide would inhibit allergic airway inflammation and influence systemic immune responses in an ovalbumin-induced asthmatic murine model. Methods The treatment effects of TNF-a antisense oligonucleotide on mice, as well as the alternative proportion of regulatory T cells and TH2 cells, were examined and compared with untreated mice. Results Local administration of TNF-a antisense oligonucleotide resulted in significantly inhibited TNF-a expression, remarkably decreased inflammatory cell infiltration and dramatically reduced mucus hypersecretion. These treatment effects were associated with induced CD4+CD25+Foxp3+ regulatory T cells, reduced TH2 cells and generally decreased TH2-type cytokines expression in bronchoalveolar lavage fluid. Systemic immunosuppression was not triggered by local antisense oligonucleotide administration because the proportion of CD4+CD25+Foxp3+ regulatory T cells in the blood, thymus or spleen was not affected. Attenuated 4-1BBL expression was likely involved in the alternative proportion of T cells. Conclusions These findings demonstrate that local administration of TNF-a antisense oligonucleotide contributes to anti-inflammatory action via the enhancement of regulatory T cells-mediated immune tolerance, which is not accompanied by systemic immunosuppression associated with systemically-induced regulatory T cells. Copyright (c) 2012 John Wiley & Sons, Ltd.
Details
- Title: Subtitle
- Locally instilled tumor necrosis factor-alpha antisense oligonucleotide inhibits allergic inflammation via the induction of Tregs
- Creators
- Yi Luo - Nanjing UniversityZhonghua Pang - Nanjing UniversityQian Zhu - Nanjing UniversityXing Cai - Nanjing UniversityYuan Yin - Nanjing UniversityMin Wang - Nanjing UniversityJie Zhu - Nanjing UniversityJiangning Chen - Nanjing UniversityKe Zeng - Nanjing UniversityChenyu Zhang - Nanjing UniversityJunfeng Zhang - Nanjing University
- Resource Type
- Journal article
- Publication Details
- The journal of gene medicine, Vol.14(6), pp.374-383
- Publisher
- Wiley
- DOI
- 10.1002/jgm.2631
- PMID
- 22576979
- ISSN
- 1099-498X
- eISSN
- 1521-2254
- Number of pages
- 10
- Grant note
- BK 2009237 / Natural Science Fund for Colleges and Universities in Jiangsu Province 01005 / Key Program for Science and Technology Research from Chinese Ministry of Education 2006AA02Z177 / Chinese National Programs for High Technology Research and Development (863 Program); National High Technology Research and Development Program of China 30771036; BK2007144; 31071232 / National Natural Science Foundation of China; National Natural Science Foundation of China (NSFC) 2009ZX09503-028 / National Key Pharmaceutical Program 20080431077; 200801364 / China Postdoctoral Science Foundation 81025019 / National Science Fund for Distinguished Young Scholars; National Natural Science Foundation of China (NSFC)
- Language
- English
- Date published
- 06/01/2012
- Academic Unit
- Urology
- Record Identifier
- 9984320853802771
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