Intranasal Administration of Lentiviral miR-135a Regulates Mast Cell and Allergen-Induced Inflammation by Targeting GATA-3
| Autor: | Yuqin Deng, Fen Li, Ya-Qi Yang, Meng-Zhi Liu, Zezhang Tao, Shui-Bin Wang, Qing-Quan Hua |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Ovalbumin
Genetic Vectors lcsh:Medicine Gene Expression Spleen Inflammation GATA3 Transcription Factor Biology Flow cytometry Th2 Cells Downregulation and upregulation medicine Animals Mast Cells lcsh:Science Administration Intranasal Mice Inbred BALB C Multidisciplinary Microscopy Confocal medicine.diagnostic_test Reverse Transcriptase Polymerase Chain Reaction lcsh:R Lentivirus Degranulation Allergens Th1 Cells Mast cell Flow Cytometry Rhinitis Allergic MicroRNAs Nasal Mucosa medicine.anatomical_structure Immunology Cancer research biology.protein lcsh:Q Nasal administration medicine.symptom T-Box Domain Proteins Research Article |
| Zdroj: | PLoS ONE PLoS ONE, Vol 10, Iss 9, p e0139322 (2015) |
| ISSN: | 1932-6203 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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