Exp Mol Med.  2011 Apr;43(4):197-204. 10.3858/emm.2011.43.4.024.

Silencing IL-23 expression by a small hairpin RNA protects against asthma in mice

• Li Y
• Sun M
• Cheng H
• Li S
• Liu L
• Qiao H
• Hua S
• Lu J

• KMID: 1104389
• DOI: http://doi.org/10.3858/emm.2011.43.4.024

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.

Keyword

asthma; interleukin-23; mice; ovalbumin; RNA interference

MeSH Terms

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