Clin Exp Otorhinolaryngol.  2015 Sep;8(3):243-249. 10.3342/ceo.2015.8.3.243.

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

• KMID: 2117519
• DOI: http://doi.org/10.3342/ceo.2015.8.3.243

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-gamma]), Th2 cytokines (interleukin [IL] 4 and IL-5) and Treg (Foxp3, IL-10, and transforming growth factor-beta [TGF-beta]) 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-gamma was unchanged in the treatment group. The levels of Foxp3, IL-10, and TGF-beta 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.

Keyword

Allergic Rhinitis; Trichostatin A; Histone Deacetylases; Ovalbumin; Mice

MeSH Terms

Animals
Cytokines
Enzyme-Linked Immunosorbent Assay
Eosinophils
Histone Deacetylases
Immunoglobulin E
Inflammation
Interleukin-10
Interleukin-4
Interleukin-5
Mice
Nasal Mucosa
Ovalbumin
Ovum
Rhinitis*
Sneezing
T-Lymphocytes, Regulatory
Transforming Growth Factor beta
Cytokines
Histone Deacetylases
Immunoglobulin E
Interleukin-10
Interleukin-4
Interleukin-5
Ovalbumin
Transforming Growth Factor beta

Figure

• 

  Fig. 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.

• 

  Fig. 2 Nasal symptom scores. (A) Rubbing score. (B) Sneezing score. OVA, ovalbumin; TSA, trichostatin A. *P<0.05 and **P<0.01 compared to control. †P<0.05 compared to OVA.

• 

  Fig. 3 Serum OVA-specific IgE levels. Serum OVA-specific IgE levels were measured by enzyme-linked immunosorbent assay. Increased level of serum OVA-specific IgE in OVA group was decreased in OVA+TSA group. OVA, ovalbumin; TSA, trichostatin A. *P<0.05 compared with control. †P<0.05 compared with OVA.

• 

  Fig. 4 Infiltration of eosinophils in the nasal mucosa. (A) Chromotrophe 2R staining of the nasal mucosa in each group. Level of eosinophil infiltration (red color) markedly decreased in OVA+TSA group compared with OVA group. (B) Eosinophil counts in the nasal mucosa. Eosinophil count was significantly reduced in OVA+TSA group compared with OVA group (×400). OVA, ovalbumin; TSA, trichostatin A. *P<0.05 compared to control. †P<0.05 compared to OVA.

• 

  Fig. 5 IFN-γ, IL-4, and IL-5 expression levels. Messenger RNA levels of IFN-γ (A), IL-4 (C), and IL-5 (E) were measured by quantitative reverse transcription-polymerase chain reaction. Protein levels of IFN-γ (B), IL-4 (D), and IL-5 (F) were measured by enzyme-linked immunosorbent assay. Levels of IL-4 and IL-5 were inhibited in OVA+TSA group compared with OVA group. However, IFN-γ level did not increase in OVA group. IFN-γ, interferon-gamma; IL, interleukin; OVA, ovalbumin; TSA, trichostatin A. *P<0.05 compared to controls. †P<0.05 compared to OVA.

• 

  Fig. 6 Activation of regulatory T cells. (A) mRNA level of Foxp3 was analyzed by quantitative reverse transcription-polymerase chain reaction. Protein levels of IL-10 (B) and TGF-β (C) were significantly increased in OVA+TSA group, as measured by enzyme-linked immunosorbent assay. OVA, ovalbumin; TSA, trichostatin A; IL, interleukin; TGF-β, transforming growth factor-beta. *P<0.05 and **P<0.01 compared to controls.

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