Silencing IL-23 expression by a small hairpin RNA protects against asthma in mice.
10.3858/emm.2011.43.4.024
- Author:
Yanchun LI
1
;
Meng SUN
;
Huanji CHENG
;
Shanyu LI
;
Li LIU
;
Hongmei QIAO
;
Shucheng HUA
;
Jirong LU
Author Information
1. Department of Pediatrics, The First Hospital of Jilin University, Changchun, Jilin, 130021, China. lujirong1103@yahoo.com.cn
- Publication Type:Original Article
- Keywords:
asthma;
interleukin-23;
mice;
ovalbumin;
RNA interference
- MeSH:
Animals;
Asthma/chemically induced/genetics/metabolism/*prevention & control;
Bronchoalveolar Lavage Fluid/cytology;
Enzyme-Linked Immunosorbent Assay;
Eosinophils;
Female;
Inflammation/metabolism;
Interleukin-23/*genetics;
Leukocyte Count;
Mice;
Mice, Inbred BALB C;
Neutrophils;
Ovalbumin/pharmacology;
Plasmids/genetics;
*RNA Interference;
RNA, Small Interfering/*genetics;
Reverse Transcriptase Polymerase Chain Reaction;
Th17 Cells/immunology
- From:Experimental & Molecular Medicine
2011;43(4):197-204
- CountryRepublic of Korea
- Language:English
-
Abstract:
To determine the impact of IL-23 knockdown by RNA interference on the development and severity of ovalbumin (OVA)-induced asthmatic inflammation, and the potential mechanisms in mice, the IL-23-specific RNAi-expressing pSRZsi-IL-23p19 plasmid was constructed and inhaled into OVA-sensitized mice before each challenge, as compared with that of control mice treated with alum or budesonide. Inhalation of the pSRZsi-IL-23p19, significantly reduced the levels of OVA-challenge induced IL-23 in the lung tissues by nearly 75%, determined by RT-PCR. In addition, knockdown of IL-23 expression dramatically reduced the numbers of eosinophils and neutrophils in BALF and mitigated inflammation in the lungs of asthmatic mice. Furthermore, knockdown of IL-23 expression significantly decreased the levels of serum IgE, IL-23, IL-17, and IL-4, but not IFNgamma, and its anti-inflammatory effects were similar to or better than that of treatment with budesonide in asthmatic mice. Our data support the notion that IL-23 and associated Th17 responses contribute to the pathogenic process of bronchial asthma. Knockdown of IL-23 by RNAi effectively inhibits asthmatic inflammation, which is associated with mitigating the production of IL-17 and IL-4 in asthmatic mice.
