title: Adenovirus-mediated delivery of soluble ST2 attenuates ovalbumin-induced allergic asthma in mice.
abstract: 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.
authors.affiliation: Department of Microbiology and Immunology, Guangdong Pharmaceutical University, Guangzhou, China.
authors.forename: H
authors.initials: H
authors.lastname: Yin
authors.forename: X Y
authors.initials: XY
authors.lastname: Li
authors.forename: T
authors.initials: T
authors.lastname: Liu
authors.forename: B H
authors.initials: BH
authors.lastname: Yuan
authors.forename: B B
authors.initials: BB
authors.lastname: Zhang
authors.forename: S L
authors.initials: SL
authors.lastname: Hu
authors.forename: H B
authors.initials: HB
authors.lastname: Gu
authors.forename: X B
authors.initials: XB
authors.lastname: Jin
authors.forename: J Y
authors.initials: JY
authors.lastname: Zhu
mesh_terms: D000256:Adenoviridae; D000281:Administration, Intranasal; D000485:Allergens / Q000276:immunology; D000818:Animals; D001249:Asthma / Q000628:therapy*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D004804:Eosinophils / Q000276:immunology / Q000378:metabolism; D005260:Female; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000008:administration & dosage*; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology / Q000628:therapy; D007073:Immunoglobulin E / Q000097:blood / Q000187:drug effects; D000072179:Interleukin-1 Receptor-Like 1 Protein; D018793:Interleukin-13 / Q000032:analysis / Q000378:metabolism; D000067596:Interleukin-33; D015847:Interleukin-4 / Q000032:analysis / Q000378:metabolism; D015848:Interleukin-5 / Q000032:analysis / Q000378:metabolism; D007378:Interleukins / Q000037:antagonists & inhibitors / Q000378:metabolism; D008168:Lung / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000276:immunology; D018123:Receptors, Interleukin / Q000235:genetics*; D017472:Receptors, Interleukin-1 / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000235:genetics; D018418:Th2 Cells / Q000276:immunology
chemical_list: D000485:Allergens; C506536:IL33 protein, human; C486189:Il1rl1 protein, mouse; D000072179:Interleukin-1 Receptor-Like 1 Protein; D018793:Interleukin-13; D000067596:Interleukin-33; D015848:Interleukin-5; D007378:Interleukins; D018123:Receptors, Interleukin; D017472:Receptors, Interleukin-1; D011993:Recombinant Fusion Proteins; C530318:ST2L protein, mouse; D015847:Interleukin-4; D007073:Immunoglobulin E; D010047:Ovalbumin