title: Intranasal Administration of Lentiviral miR-135a Regulates Mast Cell and Allergen-Induced Inflammation by Targeting GATA-3.
abstract: Mast cell (MC) degranulation is the foundation of the acute phase of allergic rhinitis (AR). Previously, downregulation of GATA binding protein 3 (GATA-3) was shown to suppress MC activation in an AR mouse model. Binding of microRNA-135a (miR-135a) to GATA-3 was also observed, and overexpression of this miRNA decreased GATA-3 mRNA and protein expression. However, the effects of miR-135a on MCs during AR are currently unknown. In the present study, we utilized a lentiviral (LV) vector to intranasally administer miR-135a to ovalbumin (OVA)-sensitized AR mice. Following miR-135a treatment, the total serum IgE concentration observed during AR was significantly reduced. In the nasal mucosa, the expression of T-box expressed in T cells (T-bet) was higher, whereas that of GATA-3 was lower in the AR mice following miRNA treatment. Notably, during AR, the ratio of type 1 T-helper cells (Th1) to type 2 (Th2) cells in the spleen is unbalanced, favoring Th2. However, administering miR-135a to the AR mice appeared to balance this ratio by increasing and decreasing the percentage of Th1 and Th2 cells, respectively. MiR-135a also appeared to strongly suppress the infiltration of eosinophils and MCs into the nasal mucosa, and it was specifically localized in the MCs, suggesting that its influence is modulated through regulation of GATA-3 in these cells. Additional work identifying the full therapeutic potential of miR-135a in the treatment of AR and diseases involving allergen-induced inflammation is warranted.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei, China.
authors.forename: Yu-Qin
authors.initials: YQ
authors.lastname: Deng
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei, China.
authors.forename: Ya-Qi
authors.initials: YQ
authors.lastname: Yang
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Yichang Yiling Hospital, Yichang, Hubei, China.
authors.forename: Shui-Bin
authors.initials: SB
authors.lastname: Wang
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei, China.
authors.forename: Fen
authors.initials: F
authors.lastname: Li
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei, China.
authors.forename: Meng-Zhi
authors.initials: MZ
authors.lastname: Liu
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei, China.
authors.forename: Qing-Quan
authors.initials: QQ
authors.lastname: Hua
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei, China.
authors.forename: Ze-Zhang
authors.initials: ZZ
authors.lastname: Tao
mesh_terms: D000281:Administration, Intranasal; D000485:Allergens / Q000276:immunology; D000818:Animals; D005434:Flow Cytometry; D050990:GATA3 Transcription Factor / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D015870:Gene Expression / Q000276:immunology; D005822:Genetic Vectors / Q000008:administration & dosage / Q000235:genetics; D016086:Lentivirus / Q000235:genetics; D008407:Mast Cells / Q000276:immunology* / Q000378:metabolism; D008807:Mice, Inbred BALB C; D035683:MicroRNAs / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D018613:Microscopy, Confocal; D009297:Nasal Mucosa / Q000276:immunology / Q000378:metabolism; D010047:Ovalbumin / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D065631:Rhinitis, Allergic / Q000235:genetics / Q000276:immunology*; D020825:T-Box Domain Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism; D000098815:T-bet Transcription Factor
chemical_list: D000485:Allergens; D050990:GATA3 Transcription Factor; C494748:Gata3 protein, mouse; D035683:MicroRNAs; C549289:Mirn135 microRNA, mouse; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; D010047:Ovalbumin