Abstract
Aim To investigate the therapeutic effect of LiuJunZi decoction (LJZD) in an experimental model of asthma and uncover its potential mechanism. Materials and Methods The ovalbumin (OVA) was applied to induce asthma in Balb/C mice, and LJZD was orally administrated to asthmatic mice. The lung function and histological lesion were evaluated by airway hyperresponsiveness assay, lung edema assay, and hematoxylin and eosin staining. The amounts of CD4+CD25+Foxp3+ TReg cells were analyzed through combining fluorescent antibody staining with flow cytometry assay. The levels of inflammatory factors and immunoglobulins were detected by enzyme-linked immuno sorbent assay (ELISA). The expression of miR-21 and miR-146a was investigated by real-time PCR. The protein expression of activating protein-1 (AP-1), nuclear factor kappa-B (NF-κB), and NF-κB inhibitor alpha (IκBα) was determined by western blotting. Results LJZD improves OVA-induced asthma in Balb/C mice, which is manifested by decreasing lung edema, Penh levels, lung histological lesion, and inflammatory cell infiltration. LJZD increased the number of CD4+CD25+Foxp3+ TReg cells in blood mononuclear cells from asthmatic mice. Furthermore, LJZD reduced the levels of tumor necrosis factor-α (TNF-α), interleukin- (IL-) 4, IL-6, IgG1, and IgE, but increased interferon gamma (IFN-γ) expression, in serum of asthmatic mice, and also decreased the expression of IL-17a, IL-23, IL-25, and thymic stromal lymphopoietin (Tslp) in lung tissues. In addition, miR-21 and miR-146a expression and phospho (p)-NF-κB, p-IκBα, and AP-1 protein expression were inhibited by LJZD in lung tissues from asthmatic mice. Conclusion LJZD improved OVA-induced asthma in Balb/C mice by inhibiting allergic inflammation and Th2 immunoreaction, which might be associated with the inactivation of the NF-κB signaling pathway.
Highlights
Asthma, characterized by the chronic inflammation, constriction, and high reactivity of the airway, has been affecting 300 million people worldwide and will have affected almost 400 million people by 2025 [1,2,3,4]
Most asthmatics suffer type 2 inflammation regulated by T-helper 2 ( 2) lymphocytes, and the 2 lymphocytes induce the secretion of lgE antibody and inflammatory cytokines, during the development of asthma [8, 9]. ese inflammatory cytokines subsequently induce the production of mucous glands, collagen deposition, and smooth muscle dysfunction in the airway, which leads to airway remodeling. e serious airway remodeling will result in the loss of lung function which will produce great economic and life burden of asthmatics
Ymus-selected CD4+CD25+forkhead box P3 (Foxp3)+ TReg cells are a subset of TReg cells which can suppress the allergic type 2 inflammation, and the decrease of these cells indicated suppressed immunologic response in peripheral blood and destructed peripheral tolerance to allergens [22]. erefore, CD4+CD25+Foxp3+ TReg cells are considered as one kind of target cells for allergen-specific immunotherapy in asthma [23]. e inflammatory cytokines tumor necrosis factor-α (TNF-α), IL-4, and IL-6 in blood can attack tissues and organs
Summary
Asthma, characterized by the chronic inflammation, constriction, and high reactivity of the airway, has been affecting 300 million people worldwide and will have affected almost 400 million people by 2025 [1,2,3,4]. Most asthmatics suffer type 2 inflammation regulated by T-helper 2 ( 2) lymphocytes, and the 2 lymphocytes induce the secretion of lgE antibody and inflammatory cytokines, during the development of asthma [8, 9]. Canadian Respiratory Journal erefore, developing safe and efficient therapeutic medicines for asthma has always been a vital concern and challenge for researchers. In TCM, multiple ingredients work on comprehensive body targets to synergistically develop the pharmaceutical effects in the treatment of asthma [13]. LJZD and its ingredients protect lung function from smoke-induced chronic obstructive pulmonary disease and improve the allergic response through regulating the physiologic function of the DC-CD4+ T-cell interaction in the dust mite allergy asthma patients [18,19,20]. LJZD and its ingredients protect lung function from smoke-induced chronic obstructive pulmonary disease and improve the allergic response through regulating the physiologic function of the DC-CD4+ T-cell interaction in the dust mite allergy asthma patients [18,19,20]. erefore, we aim to comprehensively evaluate the therapeutic effect of LJZD on asthma and identify its potential mechanism, which may provide us some enlightenment on the treatment of asthma
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