Adenovirus-mediated delivery of soluble ST2 attenuates ovalbumin-induced allergic asthma in mice

H Yin, XY Li, T Liu, BH Yuan, BB Zhang… - Clinical & …, 2012 - academic.oup.com
H Yin, XY Li, T Liu, BH Yuan, BB Zhang, SL Hu, HB Gu, XB Jin, JY Zhu
Clinical & Experimental Immunology, 2012academic.oup.com
Allergic asthma is associated with excessive T helper type 2 (Th2) cells activation and
airway hyperreactivity (AHR), implicated in the context of significant morbidity and mortality.
Soluble ST2, a member of the interleukin (IL)-1 receptor family, has been shown to play a
critical role in modulation of inflammatory disorders, yet the function of soluble ST2 in
allergic inflammation remains unclear. In this study, we examined the possibility of
regulating ovalbumin (OVA)-challenged airway inflammation by recombinant adenovirus …
Summary
Allergic asthma is associated with excessive T helper type 2 (Th2) cells activation and airway hyperreactivity (AHR), implicated in the context of significant morbidity and mortality. Soluble ST2, a member of the interleukin (IL)-1 receptor family, has been shown to play a critical role in modulation of inflammatory disorders, yet the function of soluble ST2 in allergic inflammation remains unclear. In this study, we examined the possibility of regulating ovalbumin (OVA)-challenged airway inflammation by recombinant adenovirus-mediated sST2-Fc (Ad-sST2-Fc) gene transfer. Single intranasal administration of Ad-sST2-Fc before allergen challenge in OVA-immunized mice profoundly reduced serum immunoglobulin (Ig)E secretion, eosinophil infiltration and concentrations of IL-4, IL-5 and IL-13 in bronchoalveolar lavage fluid compared with administration of a control Ad vector. Histopathological examination of the lungs revealed that sST2-Fc over-expression markedly suppressed allergen-induced peribronchial inflammation and disruption of the alveolar architecture. Moreover, the beneficial effect of sST2-Fc in allergic lung inflammation is related to blocking the IL–33/ST2L signalling. Taken together, these results suggested that administration of Ad-sST2-Fc gene transfer may have therapeutic potential for the immunomodulatory treatment of OVA-mediated allergic pulmonary diseases.
Oxford University Press