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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

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.
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Figure 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.

Mentions: In the evaluation of the allergic reaction, level of the Th1 cytokine IFN-γ showed no significant difference in all groups (Fig. 5A, B). Allergic asthmatic inflammation and remodeling are caused by the secretion of a series of Th2 cytokines, particularly IL-4 and IL-5. Therefore, we examined whether the levels of these cytokine were altered in OVA+TSA-treated mice. IL-4 and IL-5 levels in the OVA group were significantly higher than in the control group. However, the levels of IL-4 and IL-5 cytokines were significantly reduced in the OVA+TSA group (Fig. 5C-F).


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)

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.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 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.
Mentions: In the evaluation of the allergic reaction, level of the Th1 cytokine IFN-γ showed no significant difference in all groups (Fig. 5A, B). Allergic asthmatic inflammation and remodeling are caused by the secretion of a series of Th2 cytokines, particularly IL-4 and IL-5. Therefore, we examined whether the levels of these cytokine were altered in OVA+TSA-treated mice. IL-4 and IL-5 levels in the OVA group were significantly higher than in the control group. However, the levels of IL-4 and IL-5 cytokines were significantly reduced in the OVA+TSA group (Fig. 5C-F).

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