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 IFNγ, 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.

αβ T cells and a mixed Th1/Th17 response are important in organic dust-induced airway disease

“…IL-23 was not different between groups, which may be due to the time interval investigated or represents a distinction from other lung inflammatory models such as asthma whereby IL-23 and IL-17A are important in the enhancement and maintenance of eosinophilic and neutrophilic inflammatory responses. 24–27 A similar Th1/Th17 response was demonstrated following repetitive PGN exposures, supporting a role for microbial components like PGN in driving organic dust-induced airway inflammatory responses. Our findings of a mixed Th1/Th17 response would be consistent with observations in smoking subjects with chronic obstructive lung disease (COPD).…”

IL-23, rather than IL-17, is crucial for the development of ovalbumin-induced allergic rhinitis

“…To date, the contribution of IL-23 and IL-17 to asthma is controversial, with different studies proposing either a pathogenic (Haworth et al, 2008;Li et al, 2011;Wakashin et al, 2008) or a protective role (Schnyder-Candrian et al, 2006). Wang et al (2013) reported that IL-17 has a pathogenic role in this wellestablished mouse model of AR, and its effects are limited to the Th2 responses, nasal neutrophil and eosinophil infiltration.…”

CD80 and CD86 knockdown in dendritic cells regulates Th1/Th2 cytokine production in asthmatic mice

“…The ability of RNAi to inhibit virulent gene expression has been widely used to treat a variety of diseases (33)(34)(35). Also, a number of studies have reported that RNAi can be used in DCs to diagnose and treat bronchial asthma (36)(37)(38)(39). Darcan-Nicolaisen et al (40) discovered that the two major signs of allergic asthma in the OVA-induced asthma mouse model, which are airway inflammation and hyperactivity, were significantly ameliorated by signal transducer and activator of transcription 6 (STAT6) silencing in airway epithelial cells using the administration of siRNA nose drops.…”