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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

Lentiviral-mmu-miR-135a is expressed in mast cells.Laser scanning confocal microscopy (original magnification × 400) was used to analyze the expression of lentiviral-mmu-miR-135a (green; A) and tryptase (red; B) in mast cells present in the nasal mucosa of the positive group. Cell nuclei were stained with DAPI (blue; C). The merged image (D) highlights the overlapped green and red signals around the mast cell nuclei.
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pone.0139322.g008: Lentiviral-mmu-miR-135a is expressed in mast cells.Laser scanning confocal microscopy (original magnification × 400) was used to analyze the expression of lentiviral-mmu-miR-135a (green; A) and tryptase (red; B) in mast cells present in the nasal mucosa of the positive group. Cell nuclei were stained with DAPI (blue; C). The merged image (D) highlights the overlapped green and red signals around the mast cell nuclei.

Mentions: Laser scanning confocal microscopy was used to determine whether LV miR-135a localized specifically in the MCs of treated AR mice. As shown in Fig 8, the expression of miR-135a in the nasal mucosa after treatment with the LV miR-135a vector overlapped with expression of tryptase. These results suggest that LV miR-135a expression is MC.


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)

Lentiviral-mmu-miR-135a is expressed in mast cells.Laser scanning confocal microscopy (original magnification × 400) was used to analyze the expression of lentiviral-mmu-miR-135a (green; A) and tryptase (red; B) in mast cells present in the nasal mucosa of the positive group. Cell nuclei were stained with DAPI (blue; C). The merged image (D) highlights the overlapped green and red signals around the mast cell nuclei.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0139322.g008: Lentiviral-mmu-miR-135a is expressed in mast cells.Laser scanning confocal microscopy (original magnification × 400) was used to analyze the expression of lentiviral-mmu-miR-135a (green; A) and tryptase (red; B) in mast cells present in the nasal mucosa of the positive group. Cell nuclei were stained with DAPI (blue; C). The merged image (D) highlights the overlapped green and red signals around the mast cell nuclei.
Mentions: Laser scanning confocal microscopy was used to determine whether LV miR-135a localized specifically in the MCs of treated AR mice. As shown in Fig 8, the expression of miR-135a in the nasal mucosa after treatment with the LV miR-135a vector overlapped with expression of tryptase. These results suggest that LV miR-135a expression is MC.

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