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Intranasal Administration of Lentiviral miR-135a Regulates Mast Cell and Allergen-Induced Inflammation by Targeting GATA-3.

Deng YQ, Yang YQ, Wang SB, Li F, Liu MZ, Hua QQ, Tao ZZ - PLoS ONE (2015)

Bottom Line: However, the effects of miR-135a on MCs during AR are currently unknown.Following miR-135a treatment, the total serum IgE concentration observed during AR was significantly reduced.Additional work identifying the full therapeutic potential of miR-135a in the treatment of AR and diseases involving allergen-induced inflammation is warranted.

View Article: PubMed Central - PubMed

Affiliation: Department of Otolaryngology-Head and Neck Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei, China.

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.

No MeSH data available.


Related in: MedlinePlus

Expression of miR-135a in the nasal mucosa of AR mice following treatment with lentiviral-mmu-miR-135a.RT-qPCR was used to evaluate the relative expression levels of miR-135a in the nasal mucosa of mice in the normal (control), AR (AR-induced), positive (AR-induced, treated with lentiviral-mmu-miR-135a), and negative (AR-induced, treated with empty lentivirus) groups. Data are presented as the mean ± SEM. *P<0.05.
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pone.0139322.g003: Expression of miR-135a in the nasal mucosa of AR mice following treatment with lentiviral-mmu-miR-135a.RT-qPCR was used to evaluate the relative expression levels of miR-135a in the nasal mucosa of mice in the normal (control), AR (AR-induced), positive (AR-induced, treated with lentiviral-mmu-miR-135a), and negative (AR-induced, treated with empty lentivirus) groups. Data are presented as the mean ± SEM. *P<0.05.

Mentions: In our previous study, we found that miR-135a specifically base pairs to the 3′-UTR of GATA-3 mRNA and is downregulated during AR in our mouse model 12. To further understand the role of miR-135a during AR in the present investigation, we sought to overexpress miR-135a in the nasal mucosa of AR-induced mice via intranasal infection with an LV vector containing miR-135a. Notably, after AR mice were treated with LV miR-135a (positive group), miR-135a was significantly upregulated, indicating successful LV-host gene transduction in the nasal passages of these mice (Fig 3). In contrast, miR-135a expression in the negative and AR groups was significantly lower than that in the normal group and positive groups.


Intranasal Administration of Lentiviral miR-135a Regulates Mast Cell and Allergen-Induced Inflammation by Targeting GATA-3.

Deng YQ, Yang YQ, Wang SB, Li F, Liu MZ, Hua QQ, Tao ZZ - PLoS ONE (2015)

Expression of miR-135a in the nasal mucosa of AR mice following treatment with lentiviral-mmu-miR-135a.RT-qPCR was used to evaluate the relative expression levels of miR-135a in the nasal mucosa of mice in the normal (control), AR (AR-induced), positive (AR-induced, treated with lentiviral-mmu-miR-135a), and negative (AR-induced, treated with empty lentivirus) groups. Data are presented as the mean ± SEM. *P<0.05.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4587974&req=5

pone.0139322.g003: Expression of miR-135a in the nasal mucosa of AR mice following treatment with lentiviral-mmu-miR-135a.RT-qPCR was used to evaluate the relative expression levels of miR-135a in the nasal mucosa of mice in the normal (control), AR (AR-induced), positive (AR-induced, treated with lentiviral-mmu-miR-135a), and negative (AR-induced, treated with empty lentivirus) groups. Data are presented as the mean ± SEM. *P<0.05.
Mentions: In our previous study, we found that miR-135a specifically base pairs to the 3′-UTR of GATA-3 mRNA and is downregulated during AR in our mouse model 12. To further understand the role of miR-135a during AR in the present investigation, we sought to overexpress miR-135a in the nasal mucosa of AR-induced mice via intranasal infection with an LV vector containing miR-135a. Notably, after AR mice were treated with LV miR-135a (positive group), miR-135a was significantly upregulated, indicating successful LV-host gene transduction in the nasal passages of these mice (Fig 3). In contrast, miR-135a expression in the negative and AR groups was significantly lower than that in the normal group and positive groups.

Bottom Line: However, the effects of miR-135a on MCs during AR are currently unknown.Following miR-135a treatment, the total serum IgE concentration observed during AR was significantly reduced.Additional work identifying the full therapeutic potential of miR-135a in the treatment of AR and diseases involving allergen-induced inflammation is warranted.

View Article: PubMed Central - PubMed

Affiliation: Department of Otolaryngology-Head and Neck Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei, China.

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.

No MeSH data available.


Related in: MedlinePlus