ABSTRACT
Bronchial asthma is characterized by chronic lung inflammation, airway hyperresponsiveness, and airway remodelling. Astragaloside IV (3-O-ß-D-xylopyranosyl-6-O-ß-D-glucopyranosyl-cycloastragenol, AST), the primary pure saponin isolated from the root of Astragalus membranaceus, is an effective compound with distinct pharmacological effects including anti-inflammation, immunoregulation, and antifibrosis. However, the effect of AST on asthma remains unclear. In the present study, in the murine model of asthma, the airway hyperresponsiveness was relieved after treatment with AST, accompanied by a reduction of inflammatory cells. In addition, the levels of IL-4 and IL-5 decreased, while the IFN-γ level increased, in bronchoalveolar lavage fluid. The compound also significantly inhibited the synthesis of GATA-3-encoding mRNA and protein in addition to increasing the synthesis of T-bet-encoding mRNA and protein in both lung tissues and CD4+ T cells. Our findings indicate that AST treatment inhibits ovalbumin-induced airway inflammation by modulating the key master switches GATA-3 and T-bet, which results in committing T helper cells to a Th1 phenotype.
Subject(s)
Asthma/prevention & control , Astragalus propinquus/chemistry , Bronchial Hyperreactivity/prevention & control , Saponins/pharmacology , Triterpenes/pharmacology , Animals , Asthma/immunology , Asthma/physiopathology , Bronchial Hyperreactivity/immunology , Bronchoalveolar Lavage Fluid , Disease Models, Animal , Female , GATA3 Transcription Factor/genetics , Interferon-gamma/immunology , Interleukin-4/immunology , Interleukin-5/immunology , Male , Mice , Mice, Inbred BALB C , Ovalbumin/immunology , Pneumonia/immunology , Pneumonia/prevention & control , RNA, Messenger/metabolism , Saponins/isolation & purification , Triterpenes/isolation & purificationABSTRACT
OBJECTIVE: To investigate the expression of the T cell-specific transcription factors T-bet/GATA-3 in recurrent aphthous ulcerations (RAU). METHODS: Peripheral blood mononuclear cells (PBMC) were isolated by density gradient centrifugation from RAU patients and healthy controls. Expressions of T-bet and GATA-3 mRNA and protein in the PBMCs were detected by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot respectively. The concentrations of gamma-interferon (gamma-IFN) and interleukin-4 (IL-4) in the serum were determined by enzyme-linked immunosorbent assay (ELISA). RESULTS: The expressions of T-bet mRNA were 0.73 +/- 0.14 in the control group and 0.12 +/- 0.04 in the recurrent aphthous ulcerations group, the levels of T-bet protein expressions were 0.73 +/- 0.18 in the control group and 0.24 +/- 0.09 in the recurrent aphthous ulcerations group, there was a significant difference between the two groups (P < 0.01). The levels of GATA-3 mRNA expressions were 0.89 +/- 0.11 in the control group and 1.30 +/- 0.13 in the recurrent aphthous ulcerations group; GATA-3 protein expressions were 1.09 +/- 0.16 in the control group and 1.80 +/- 0.16 in the recurrent aphthous ulcerations group, there was a significant difference between the two groups (P < 0.01). In the control group, the concentration of gamma-interferon in the serum was (22.15 +/- 1.52) ng/L, which was significantly elevated compared with that in the recurrent aphthous ulcerations group (16.32 +/- 0.22) ng/L (P < 0.01), in the control group, the concentration of IL-4 in the serum was (25.58 +/- 2.59) ng/L, which was significantly lower than that of the recurrent aphthous ulcerations group (43.60 +/- 3.15) ng/L (P < 0.01). The ratio of gamma-IFN and IL-4 was positively correlated with the ratio of T-bet and GATA-3 mRNA and protein expression (r = 0.96, 0.94, P < 0.01). CONCLUSIONS: Imbalance of transcription factors T-bet and GATA-3 may be one of the key factors in immune dysregulation of recurrent aphthous ulcerations.
