RESUMEN
Allergic airway inflammation is one of the major pathological events involved in the development of asthma. The B cell-activating factor (BAFF)-mediated abnormal activation of B cells plays a key role in developing allergic airway inflammation. Here, we investigated the effects of Gu-Ben-Fang-Xiao decoction (GBFXD), a TCM decoction used in the prevention and treatment of allergic asthma, on allergic airway inflammation and BAFF-mediated B cell activation. A mouse model of OVA-Severe respiratory syncytial virus (RSV) induced asthma in the remission stage was administrated with GBFXD by gavage for four weeks, after which, the pulmonary function was evaluated. Pathological changes of the lung were observed by hematoxylin and eosin (HE) staining, and serum levels of IgE, BAFF, and inflammatory factors were detected by ELISA. The expression of BAFF, APRIL, and their related receptors in the lung and spleen was detected by Western blotting and RT-qPCR. Flow cytometry detected B cell subsets in the spleen, PBC, and monocyte subsets in bronchoalveolar lavage fluid (BALF). The results showed that GBFXD improved the lung function, alleviated the inflammatory changes of the lung tissue in OVA-RSV sensitized mice, and reduced levels of IL-6, TNF-α, IL1-ß, INOS, IL13 as well as IL-15, IgE, BAFF in the serum of OVA-RAV mice. Additionally, GBFXD significantly reduced the proportion of CD19+CD27+ B cell subpopulation and IgEâ¯+â¯B cell subpopulation in the PBC and spleen cells of mice. Furthermore, the expression of BAFF, APRIL, BAFFR, TACI, and AID decreased in the lung and spleen of GBFXD-treated mice, as well as the proportion of CD11bâ¯+â¯BAFFâ¯+â¯cell subsets in BALF. In conclusion, GBFXD has an inhibitory effect on the secretion of BAFF by pulmonary macrophages and the expression of BAFF-related receptors, thereby reducing B cell activation and the release of IgE. This proposed mechanism contributes to the improvement of allergic airway inflammation and respiratory function in an asthmatic mouse model.
Asunto(s)
Asma/tratamiento farmacológico , Factor Activador de Células B/metabolismo , Medicamentos Herbarios Chinos/farmacología , Inflamación/tratamiento farmacológico , Animales , Asma/inmunología , Linfocitos B/inmunología , Líquido del Lavado Bronquioalveolar/citología , Modelos Animales de Enfermedad , Femenino , Inflamación/inmunología , Pulmón/efectos de los fármacos , Pulmón/inmunología , Pulmón/patología , Ratones , Ratones Endogámicos BALB C , Ovalbúmina/inmunología , Virus Sincitiales Respiratorios/inmunologíaRESUMEN
PURPOSE: Clematis chinensis Osbeck (CCO) is an essential herb that has been shown to promote the biological functions of cartilage cells. In this study, we aimed to explore whether and how low-intensity pulsed ultrasound (LIPUS) enhanced CCO delivery into chondrocytes and stimulated biological activity in vitro. METHODS: Chondrocytes were isolated from knee articular cartilage of 2-week-old rabbits and treated with LIPUS plus CCO or recombinant transforming growth factor beta 1 (TGF-ß1; 0.5 ng/mL), with or without anti-TGF-ß1 antibodies (10 µg/mL), for 3 days. Cell proliferation was assessed by Cell-Counting Kit-8 assays. Immunocytochemistry, western blotting, and quantitative polymerase chain reaction were applied to detect the expression of type II collagen and some molecules in the TGF-ß1 signal pathway. RESULTS: LIPUS plus 0.1 mg/mL CCO solution promoted chondrocyte proliferation and type II collagen and TGF-ß1 expression synergistically in vitro (P < 0.05). In addition, treatment with anti-TGF-ß1 antibodies blocked this effect (P < 0.01), but not completely. CCO plus LIPUS also showed more enhanced effects on promoting TGF-ß receptor II and Smad2 signaling and reducing Smad7 signaling than either intervention separately (P < 0.05). CONCLUSIONS: CCO plus LIPUS promoted extracellular matrix deposition by accelerating the TGF-ß/Smad-signaling pathway in chondrocytes.