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

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.

• Authors: Yanchun Li, Meng Sun, Huanji Cheng, Shanyu Li, Li Liu, Hongmei Qiao, Shucheng Hua, Jirong Lu
• Journal: Experimental & molecular medicine (Exp Mol Med) Vol. 43 Issue 4 Pg. 197-204 (Apr 30 2011) ISSN: 2092-6413 [Electronic] United States
• PMID: 21372631 (Publication Type: Journal Article)

Chemical References

• Interleukin-23
• RNA, Small Interfering
• Ovalbumin

Topics

• 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)