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IL-27 Administration Via Nasal Improves OVA-Induced Airway Inflammation By GADD45 but Not STAT1 Pathway
Sunday, March 6, 2016
South Exhibit Hall H (Convention Center)
Zhihong Chen, Xiaoqiong Su, MD PhD, Xiangdong Wang, Nian Dong
Rationale: IL-27 is a family member of Th1 type cytokines, which could promote Th1 development and inhibit Th2 and Th17 development at the same time. Asthma is Th2-prone chronic airway inflammation. In this study, animal models were set up to observe whether IL-27 intervention could diminish allergic airway inflammation and the related molecular mechanisms.

Methods: Two kinds of IL-27 intervention were set up, one of which is low-dose-multiple preventive model, the other is high-dose-few times treating model. Airway hyperresponsiveness BAL, HE staining were tested. The mRNA, protein level of STAT1 and GADD45γ were measured through qPCR and western blot.

Results:  In low-dose-multiple prevention group, IL-27 inhibits inflammation around bronchial and vascular obviously.  In asthma model, OVA-induced airway inflammation impaired both STAT1 phosphorylation and GADD45γ expression which mediate IFN-r producing pathway in the end. IL-27 administration by nasal pre-OVA sensitization could reverse GADD45γ impairment but not STAT1 phosphorylation. At the same time, IL-27 has little effect on alleviating airway inflammation when used post-OVA sensitization.

Conclusions: IL-27 inhibits naïve CD4+ T cells’ Th2 differentiation but not already committed Th2 cell reprogramming. Our model demonstrated IL-27 resistance when used post-OVA sensitization due to existed Th2- induced STAT1 and GADD45γ downregulation. Low-dose-multiple preventive way improve airway inflammation greatly by reversing GADD45γ expression but not STAT1-Py which indicate intervention time-point is critically important in modulating Th1-Th2 balance when using cytokine strategy.