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Published on: November 3, 2014
Effect of Blocking the OX40/OX40L Signaling Pathway by siRNA Interference on Animal Experimental Study of Allergic
Zhuo-Ping Liang1, Wei Xu1, Fei-Peng Zhao1
1Department of Otolaryngology Head and Neck Surgery, the Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, China.
Background:
The identification of new approaches and intervention targets for the treatment of AR is urgently needed. We aimed to investigate the effect of blocking the OX40/OX40L signaling pathway by small interfering RNA (siRNA) on ovalbumin (OVA)-induced AR in a mouse model.
Methods:
After establishment of the AR model, the mice were interfered by siRNA-OX40L (experimental group), siRNA-C (negative control group), or PBS (control group). Nose scratching, sneezing and nasal discharge were observed. OX40L mRNA and protein and the IL-5, TNF-α, regulatory T cell (Treg) -specific marker Foxp3, and eosinophil (EOS) levels were analyzed.
Results:
The numbers of nose scratching and sneezing were significantly lower in the siRNA-OX40L-treated group (p <0.05). After the intervention of siRNA-OX40L, OX40L mRNA and protein levels were significantly inhibited (p <0.05), but the Foxp3 level was significantly increased in the experimental group (p <0.05). The IL-5 and TNF-α levels were significantly lower in the experimental group (p <0.05), and the reduction was more evident for the Th2-type cytokine IL-5 than for the Th1-type cytokine TNF-α. Few or no EOSs were found in the nasal mucosal epithelium of the experimental group (p <0.05), whereas EOS infiltration was significant in the other two groups.
Conclusions:
Blockage of the OX40/OX40L signaling pathway with siRNA-OX40L interference can inhibit allergic reactions and relieve allergic symptoms in AR mice. The underlying mechanism may be related to correcting Th2 immune deviation, inducing immune tolerance, and promoting Treg production.
Insights
Blocking the OX40/OX40L pathway with siRNA-OX40L significantly reduced allergic rhinitis symptoms in mice. This approach may correct immune imbalance and promote immune tolerance for treating allergic rhinitis.
Area of Science:
- Immunology
- Allergy Research
Background:
- Allergic rhinitis (AR) necessitates novel therapeutic targets.
- Investigating the OX40/OX40L signaling pathway as a potential intervention point for AR.
Purpose of the Study:
- To evaluate the efficacy of blocking the OX40/OX40L signaling pathway using small interfering RNA (siRNA) in a mouse model of ovalbumin (OVA)-induced allergic rhinitis.
Main Methods:
- Established an allergic rhinitis mouse model.
- Intervened with siRNA-OX40L, a negative control siRNA, or PBS.
- Assessed allergic symptoms (nose scratching, sneezing, nasal discharge) and analyzed levels of OX40L, IL-5, TNF-α, Foxp3, and eosinophils (EOS).
Main Results:
- siRNA-OX40L treatment significantly reduced allergic symptoms and OX40L expression.
- Increased Foxp3 levels and decreased IL-5 and TNF-α levels were observed in the siRNA-OX40L group.
- Significantly reduced eosinophil infiltration in the nasal mucosa of the treated group.
Conclusions:
- Blocking the OX40/OX40L pathway with siRNA-OX40L effectively inhibits allergic reactions and alleviates symptoms in AR mice.
- Potential mechanisms include correcting Th2 immune deviation, inducing immune tolerance, and promoting regulatory T cell (Treg) production.
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