PMID- 26418311 OWN - NLM STAT- MEDLINE DCOM- 20160531 LR - 20220316 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 10 IP - 9 DP - 2015 TI - Intranasal Administration of Lentiviral miR-135a Regulates Mast Cell and Allergen-Induced Inflammation by Targeting GATA-3. PG - e0139322 LID - 10.1371/journal.pone.0139322 [doi] LID - e0139322 AB - 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. FAU - Deng, Yu-Qin AU - Deng YQ AD - Department of Otolaryngology-Head and Neck Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei, China. FAU - Yang, Ya-Qi AU - Yang YQ AD - Department of Otolaryngology-Head and Neck Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei, China. FAU - Wang, Shui-Bin AU - Wang SB AD - Department of Otolaryngology-Head and Neck Surgery, Yichang Yiling Hospital, Yichang, Hubei, China. FAU - Li, Fen AU - Li F AD - Department of Otolaryngology-Head and Neck Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei, China. FAU - Liu, Meng-Zhi AU - Liu MZ AD - Department of Otolaryngology-Head and Neck Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei, China. FAU - Hua, Qing-Quan AU - Hua QQ AD - Department of Otolaryngology-Head and Neck Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei, China. FAU - Tao, Ze-Zhang AU - Tao ZZ AD - Department of Otolaryngology-Head and Neck Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20150929 PL - United States TA - PLoS One JT - PloS one JID - 101285081 RN - 0 (Allergens) RN - 0 (GATA3 Transcription Factor) RN - 0 (Gata3 protein, mouse) RN - 0 (MicroRNAs) RN - 0 (Mirn135 microRNA, mouse) RN - 0 (T-Box Domain Proteins) RN - 0 (T-box transcription factor TBX21) RN - 9006-59-1 (Ovalbumin) SB - IM MH - Administration, Intranasal MH - Allergens/immunology MH - Animals MH - Flow Cytometry MH - GATA3 Transcription Factor/genetics/*immunology/metabolism MH - Gene Expression/immunology MH - Genetic Vectors/administration & dosage/genetics MH - Lentivirus/genetics MH - Mast Cells/*immunology/metabolism MH - Mice, Inbred BALB C MH - MicroRNAs/genetics/*immunology/metabolism MH - Microscopy, Confocal MH - Nasal Mucosa/immunology/metabolism MH - Ovalbumin/immunology MH - Reverse Transcriptase Polymerase Chain Reaction MH - Rhinitis, Allergic/genetics/*immunology MH - T-Box Domain Proteins/genetics/immunology/metabolism MH - Th1 Cells/immunology/metabolism MH - Th2 Cells/immunology/metabolism PMC - PMC4587974 COIS- Competing Interests: The authors have declared that no competing interests exist. EDAT- 2015/09/30 06:00 MHDA- 2016/06/01 06:00 PMCR- 2015/09/29 CRDT- 2015/09/30 06:00 PHST- 2015/03/20 00:00 [received] PHST- 2015/09/11 00:00 [accepted] PHST- 2015/09/30 06:00 [entrez] PHST- 2015/09/30 06:00 [pubmed] PHST- 2016/06/01 06:00 [medline] PHST- 2015/09/29 00:00 [pmc-release] AID - PONE-D-15-12215 [pii] AID - 10.1371/journal.pone.0139322 [doi] PST - epublish SO - PLoS One. 2015 Sep 29;10(9):e0139322. doi: 10.1371/journal.pone.0139322. eCollection 2015.