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Antiallergic Effects of Trichostatin A in a Murine Model of Allergic Rhinitis.

Cho JS, Kang JH, Han IH, Um JY, Park IH, Lee SH, Lee HM - Clin Exp Otorhinolaryngol (2015)

Bottom Line: TSA reduced the scores of allergic nasal symptoms and the amount of eosinophil infiltration into the nasal mucosa.TSA suppressed OVA-specific IgE levels and reduced expression of the IL-4 and IL-5.The levels of Foxp3, IL-10, and TGF-β were increased in pretreatment with TSA as compared to control group.

View Article: PubMed Central - PubMed

Affiliation: Brain Korea 21 Plus for Biomedical Science, Seoul, Korea. ; Institute for Medical Devices Clinical Trial Center, Seoul, Korea.

ABSTRACT

Objectives: Trichostatin A (TSA), an inhibitor of histone deacetylase, has been shown to play an important role in attenuating asthmatic inflammation. However, the effect of TSA in allergic rhinitis is not known. The aims of this study were to investigate the effect of TSA on allergic nasal inflammation and on the induction of regulatory T cells in a murine model of allergic rhinitis.

Methods: BALB/c mice were sensitized intraperitoneally with ovalbumin (OVA) and then challenged intranasally with OVA. TSA (1 mg/kg) was given to the treatment group, and multiple parameters of allergic responses were evaluated to determine the effects of TSA on allergic rhinitis. Allergic nasal symptom scores, including frequency of rubbing and sneezing, were checked. Eosinophil infiltrations were stained with Chromotrope 2R, and the expression levels of OVA-specific IgE, T-helper 1 (Th1) cytokine (interferon-gamma [IFN-γ]), Th2 cytokines (interleukin [IL] 4 and IL-5) and Treg (Foxp3, IL-10, and transforming growth factor-beta [TGF-β]) were measured by quantitative reverse transcription-polymerase chain reaction or enzyme-linked immunosorbent assay.

Results: TSA reduced the scores of allergic nasal symptoms and the amount of eosinophil infiltration into the nasal mucosa. TSA suppressed OVA-specific IgE levels and reduced expression of the IL-4 and IL-5. However, the expression of IFN-γ was unchanged in the treatment group. The levels of Foxp3, IL-10, and TGF-β were increased in pretreatment with TSA as compared to control group.

Conclusion: This study shows that TSA induced antiallergic effects by decreasing eosinophilic infiltration and Th2 cytokines in a murine model of allergic rhinitis via regulation of Tregs. Thus, TSA may be considered a potentially therapeutic agent in treating allergic rhinitis.

No MeSH data available.


Related in: MedlinePlus

Schematic representation of the murine model of allergic rhinitis and treatment protocol. BALB/c mice were sensitized with ovalbumin (OVA) and 1 mg of aluminum hydroxide (Alum) on days 0, 7, and 14. All groups except control received intranasal OVA from 21 days to 24 days. In addition to sensitization and challenge, TSA+OVA mice were injected with TSA (1 mg/kg/day). TSA, trichostatin A.
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Figure 1: Schematic representation of the murine model of allergic rhinitis and treatment protocol. BALB/c mice were sensitized with ovalbumin (OVA) and 1 mg of aluminum hydroxide (Alum) on days 0, 7, and 14. All groups except control received intranasal OVA from 21 days to 24 days. In addition to sensitization and challenge, TSA+OVA mice were injected with TSA (1 mg/kg/day). TSA, trichostatin A.

Mentions: All animal experiments in this study followed the guidelines for Institutional Animal Care at the Clinical Research Institute of Korea University Guro Hospital. Female BALB/c mice (weight, 18-22 g; Orient, Seongnam, Korea) were divided into three groups (6 mice/group). Control mice were sensitized and challenged with phosphate buffered saline (PBS, negative control); OVA mice were sensitized and challenged with OVA; TSA-treated, OVA+TSA mice were sensitized and treated with TSA, then challenged with OVA (OVA+TSA). Mice were sensitized with 25-µg OVA with or without 2 mg of alum hydroxide (Imject Alum, Thermo Scientific, Waltham, MA, USA) dissolved in PBS, and a total of 300 µL was injected intraperitoneally on days 0, 7, and 14. Five days after the final injection of OVA, mice were injected with TSA (1 mg/kg) by an intraperitoneal injection for six days. One week after the final injection, mice were challenged by intranasal instillation with 200 µg of OVA solubilized in PBS (10 µL/nostril) once daily for 4 days. Control mice were treated by intranasal instillation with PBS. All mice were sacrificed 24 hours after the final instillation (Fig. 1).


Antiallergic Effects of Trichostatin A in a Murine Model of Allergic Rhinitis.

Cho JS, Kang JH, Han IH, Um JY, Park IH, Lee SH, Lee HM - Clin Exp Otorhinolaryngol (2015)

Schematic representation of the murine model of allergic rhinitis and treatment protocol. BALB/c mice were sensitized with ovalbumin (OVA) and 1 mg of aluminum hydroxide (Alum) on days 0, 7, and 14. All groups except control received intranasal OVA from 21 days to 24 days. In addition to sensitization and challenge, TSA+OVA mice were injected with TSA (1 mg/kg/day). TSA, trichostatin A.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4553355&req=5

Figure 1: Schematic representation of the murine model of allergic rhinitis and treatment protocol. BALB/c mice were sensitized with ovalbumin (OVA) and 1 mg of aluminum hydroxide (Alum) on days 0, 7, and 14. All groups except control received intranasal OVA from 21 days to 24 days. In addition to sensitization and challenge, TSA+OVA mice were injected with TSA (1 mg/kg/day). TSA, trichostatin A.
Mentions: All animal experiments in this study followed the guidelines for Institutional Animal Care at the Clinical Research Institute of Korea University Guro Hospital. Female BALB/c mice (weight, 18-22 g; Orient, Seongnam, Korea) were divided into three groups (6 mice/group). Control mice were sensitized and challenged with phosphate buffered saline (PBS, negative control); OVA mice were sensitized and challenged with OVA; TSA-treated, OVA+TSA mice were sensitized and treated with TSA, then challenged with OVA (OVA+TSA). Mice were sensitized with 25-µg OVA with or without 2 mg of alum hydroxide (Imject Alum, Thermo Scientific, Waltham, MA, USA) dissolved in PBS, and a total of 300 µL was injected intraperitoneally on days 0, 7, and 14. Five days after the final injection of OVA, mice were injected with TSA (1 mg/kg) by an intraperitoneal injection for six days. One week after the final injection, mice were challenged by intranasal instillation with 200 µg of OVA solubilized in PBS (10 µL/nostril) once daily for 4 days. Control mice were treated by intranasal instillation with PBS. All mice were sacrificed 24 hours after the final instillation (Fig. 1).

Bottom Line: TSA reduced the scores of allergic nasal symptoms and the amount of eosinophil infiltration into the nasal mucosa.TSA suppressed OVA-specific IgE levels and reduced expression of the IL-4 and IL-5.The levels of Foxp3, IL-10, and TGF-β were increased in pretreatment with TSA as compared to control group.

View Article: PubMed Central - PubMed

Affiliation: Brain Korea 21 Plus for Biomedical Science, Seoul, Korea. ; Institute for Medical Devices Clinical Trial Center, Seoul, Korea.

ABSTRACT

Objectives: Trichostatin A (TSA), an inhibitor of histone deacetylase, has been shown to play an important role in attenuating asthmatic inflammation. However, the effect of TSA in allergic rhinitis is not known. The aims of this study were to investigate the effect of TSA on allergic nasal inflammation and on the induction of regulatory T cells in a murine model of allergic rhinitis.

Methods: BALB/c mice were sensitized intraperitoneally with ovalbumin (OVA) and then challenged intranasally with OVA. TSA (1 mg/kg) was given to the treatment group, and multiple parameters of allergic responses were evaluated to determine the effects of TSA on allergic rhinitis. Allergic nasal symptom scores, including frequency of rubbing and sneezing, were checked. Eosinophil infiltrations were stained with Chromotrope 2R, and the expression levels of OVA-specific IgE, T-helper 1 (Th1) cytokine (interferon-gamma [IFN-γ]), Th2 cytokines (interleukin [IL] 4 and IL-5) and Treg (Foxp3, IL-10, and transforming growth factor-beta [TGF-β]) were measured by quantitative reverse transcription-polymerase chain reaction or enzyme-linked immunosorbent assay.

Results: TSA reduced the scores of allergic nasal symptoms and the amount of eosinophil infiltration into the nasal mucosa. TSA suppressed OVA-specific IgE levels and reduced expression of the IL-4 and IL-5. However, the expression of IFN-γ was unchanged in the treatment group. The levels of Foxp3, IL-10, and TGF-β were increased in pretreatment with TSA as compared to control group.

Conclusion: This study shows that TSA induced antiallergic effects by decreasing eosinophilic infiltration and Th2 cytokines in a murine model of allergic rhinitis via regulation of Tregs. Thus, TSA may be considered a potentially therapeutic agent in treating allergic rhinitis.

No MeSH data available.


Related in: MedlinePlus