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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

Sensitization and treatment protocol.Mice in the AR, positive, and negative groups were sensitized with 100 μg of ovalbumin (OVA) and 1 mg of aluminum hydroxide on days 0, 7, and 14. On days 21–35, these mice were intranasally administered 40 μl of saline containing 400 μg of OVA (20 μl per nostril) for secondary immunization. Furthermore, within 3 h of each treatment on days 21–35, the AR group was treated with saline, whereas the positive and negative groups were nasally administered 2 × 106 infectious units (IFUs) of LV miR-135a and 2 × 106 IFUs of an empty LV vector, respectively.
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pone.0139322.g001: Sensitization and treatment protocol.Mice in the AR, positive, and negative groups were sensitized with 100 μg of ovalbumin (OVA) and 1 mg of aluminum hydroxide on days 0, 7, and 14. On days 21–35, these mice were intranasally administered 40 μl of saline containing 400 μg of OVA (20 μl per nostril) for secondary immunization. Furthermore, within 3 h of each treatment on days 21–35, the AR group was treated with saline, whereas the positive and negative groups were nasally administered 2 × 106 infectious units (IFUs) of LV miR-135a and 2 × 106 IFUs of an empty LV vector, respectively.

Mentions: The mice were intraperitoneally administered 300 μl of saline containing 100 μg OVA and 1 mg of aluminum hydroxide (Sigma-Aldrich, St. Louis, MO, USA) on days 0, 7, and 14 to promote primary sensitization. On days 21–35, mice in these three groups were intranasally sensitized with 40 μl of saline containing 400 μg of OVA (20 μl per nostril) for secondary immunization. The normal group was intraperitoneally injected with 300 μl of saline on days 0, 7, and 14, and then treated intranasally with 40 μl of saline on days 21–35 after the initial treatment (Fig 1).


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)

Sensitization and treatment protocol.Mice in the AR, positive, and negative groups were sensitized with 100 μg of ovalbumin (OVA) and 1 mg of aluminum hydroxide on days 0, 7, and 14. On days 21–35, these mice were intranasally administered 40 μl of saline containing 400 μg of OVA (20 μl per nostril) for secondary immunization. Furthermore, within 3 h of each treatment on days 21–35, the AR group was treated with saline, whereas the positive and negative groups were nasally administered 2 × 106 infectious units (IFUs) of LV miR-135a and 2 × 106 IFUs of an empty LV vector, respectively.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0139322.g001: Sensitization and treatment protocol.Mice in the AR, positive, and negative groups were sensitized with 100 μg of ovalbumin (OVA) and 1 mg of aluminum hydroxide on days 0, 7, and 14. On days 21–35, these mice were intranasally administered 40 μl of saline containing 400 μg of OVA (20 μl per nostril) for secondary immunization. Furthermore, within 3 h of each treatment on days 21–35, the AR group was treated with saline, whereas the positive and negative groups were nasally administered 2 × 106 infectious units (IFUs) of LV miR-135a and 2 × 106 IFUs of an empty LV vector, respectively.
Mentions: The mice were intraperitoneally administered 300 μl of saline containing 100 μg OVA and 1 mg of aluminum hydroxide (Sigma-Aldrich, St. Louis, MO, USA) on days 0, 7, and 14 to promote primary sensitization. On days 21–35, mice in these three groups were intranasally sensitized with 40 μl of saline containing 400 μg of OVA (20 μl per nostril) for secondary immunization. The normal group was intraperitoneally injected with 300 μl of saline on days 0, 7, and 14, and then treated intranasally with 40 μl of saline on days 21–35 after the initial treatment (Fig 1).

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