The Chinese Herbal Medicine Formula Sheng-Fei-Yu-Chuan-Tang Suppresses Th2 Responses and Increases IFN γ in Dermatophagoides pteronyssinus Induced Chronic Asthmatic Mice

Abstract

Sheng-Fei-Yu-Chuan-Tang (SFYCT), a traditional Chinese medicine formula consisting of 13 medicinal plants, has been used in the treatment of asthma. This study demonstrated the immunoregulatory effect of SFYCT on chronic allergic asthma using the Dermatophagoides-pteronyssinus- (Der p-) challenged chronic asthmatic murine model. SFYCT decreased the airway hyperresponseness (AHR), pulmonary inflammatory cell infiltration, and airway remodeling in Der p mice. SFYCT treatment decreased Der p-induced total IgE and Der-p-specific IgG1 but not IgG2a/2b Ab titer in serum of Der p mice. SFYCT also decreased Th2 cytokines, IL-4, IL-5, and IL-13, but increased IFN- γ and IL-12 in the BALF of Der p mice. TGF- β 1 and collagen production in the lung of mice were decreased by SFYCT. The mRNA expression of chemokine including Eotaxin, RANTES, and MCP-1 in the lung of Der p mice was decreased by SFYCT. In conclusion, the suppressed Der-p-induced airway inflammation, remodeling, and hyperresponseness in chronic asthma murine model are related to SFYCT inhibits Th2 responses, decreases chemokine expression and promotes IFN- γ and IL-12 production. SFYCT could show Der-p-induced Th2 responses to Th1 responses by increasing IFN- γ which is merit for clinical application on asthma patients.

Figure 1

The suppressive effects of SFYCT on airway hyperresponsiveness in repetitive Der-p-challenged mice. Methacholine-induced airway hyperresponsiveness was determined at day 3 after the last challenge. Values represent the means ± SE of 6 mice. *P < 0.05 compares with Naive group; ^# P < 0.05 compares with Der p group.

Figure 2

The effects of SFYCT on Der-p-induced airway inflammation, goblet cell hyperplasia, mucus hypersecretion, and collagen deposition in lung tissue of mice. (a) H&E stain and inflammatory score show the histopathologic change and inflamatory cell infiltration around the blood vessels of mice. (b) PAS stain shows the mucus of goblet cells in the airway of mice. Goblet cell hyperplasia and mucus plug in airway from PBS sham treated mouse and nontreated or SFYCT treated Der p mouse. (c) Collagen levels in the lung of mice were determined as described in Section 2. Values represent the means ± SE of 6 mice. *P < 0.05 compares with Naive group; ^# P < 0.05 compare with Der p group.

Figure 3

The effect of SFYCT on T-cell subsets in BALF of Der p mice. (a) CD3⁺/CD4⁺, (b) CD3⁺/CD8⁺, and (c) CD4⁺/CD25⁺ lymphocyte levels were determined by flow cytometry with immunofluorescence of monoclonal antibodies. Values represent the means ± SE of 6 mice. *P < 0.05 compares with Naïve group; ^# P < 0.05 compare with Der p group.

Figure 4

The effects of SFYCT on inflammatory mediators in the BALF of Der p mice. The levels of (a) IL-5, (b) TGF-β, (c) IL-12, (d) IL-13, (e) IL-17, and (f) IFN-γ were determined by ELISA. Values represent the means ± SE of 6 mice. *P < 0.05 compares with Naïve group; ^# P < 0.05 compares with Der p group.

Figure 5

The evaluation of cytokine secretion and the antibody titers from the sera of mice. The effects of SFYCT on IL-4, IL-5 ((a), (b)), or allergen-specific Ab concentrations (c)–(f) were evaluated at day 3 after the last challenge in the serum of Der p mice. Values represent the means ± SE of 6 mice. *P < 0.05 compares with Naïve group; ^# P < 0.05 compares with Der p group.

Figure 6

The effects of SFYCT on chemokine expression in the lung of mice. The mRNA expression of Eotaxin, RANTES, and MCP-1 in the lung of mice was evaluated by RT-PCR. β-Actin mRNA expression was included as internal control. (a) shows the representative experiment and (b) shows the quantification of mRNA levels expressed as mean ± SE (n = 6 per group). *P < 0.05 compares with Naïve group; ^# P < 0.05 compares with Der p group.