BuShenYiQi Formula strengthens Th1 response and suppresses Th2-Th17 responses in RSV-induced asthma exacerbated mice.
BACKGROUND
The prevalence of allergic asthma has been increased rapidly in recent years. About 20% of all these sufferers have experienced asthma exacerbation. Although corticosteroids and β-agonists therapy improves serious asthma symptoms, they can׳t completely cure these allergic diseases. BuShenYiQi Formula (BSYQF) has been widely used to treat bronchial asthma and its exacerbation for decades in Huashan Hospital of Fudan University, China. Nevertheless, the mechanisms of BSYQF' anti-asthmatic effects haven׳t been fully elucidated. In this study, we evaluated the involvement of Th1, Th2 and Th17 cells in the anti-asthmatic effects of BSYQF in Respiratory Syncytial Virus (RSV)-induced asthma exacerbated mice.


METHODS
BALB/c mice were challenged with ovalbumin (OVA), followed by RSV infections for establishment of asthma exacerbated model. Airway hyperresponsiveness (AHR) was examined by direct airway resistance analysis. Bronchoalveolar lavage fluid (BALF) was assessed for inflammatory cell counts and secreted levels of cytokines. Lung tissues were detected for inflammatory cell infiltration and mucus hypersecretion. Subsequently, CD4(+)T cells and alveolar macrophages were sorted and purified from mice lungs in different groups. CD4(+)T cell subpopulations including the expression levels of important transcription factors in T lymphocyte polarization were examined. In asthma exacerbation group, the purified CD4(+)T cells and macrophages were co-cultured, and the changes of co-cultured cells with BSYQF treatment were further analyzed in vitro.


RESULTS
BSYQF significantly attenuated airway hyperresponsiveness and inhibited inflammatory cell infiltration, especially for excessive infiltration of eosinophils and neutrophils. Histopathological analysis showed that BSYQF could suppress airway inflammation and RSV replication. The decreases of antigen-specific IgE, IL-4, IL-5, IL-6, IL-17a and increases of IFN-γ, IL-12 were observed in BALF, lung homogenate or serum after BSYQF treatment. We further confirmed that BSYQF could down-regulate Th2-Th17 cell proportions with lower expressions of GATA3, STAT6 and RORγT, and up-regulate Th1 cell proportion with higher expression of T-bet. And as a result of strengthened Th1-response, activated macrophages were also observed by remarkable enhancement of signature gene expressions and phagocytosis.


CONCLUSIONS
BSYQF can significantly attenuate RSV-induced asthma exacerbation. These effects may be mediated at least partially by regulating the balance between Th1 and Th2-Th17 responses.
Department of Integrative Medicine, Huashan Hospital, Fudan University, 12 Middle Urumqi Road, Shanghai 200040, China; Institute of Integrated Traditional Chinese and Western Medicine, Fudan University, 12 Middle Urumqi Road, Shanghai 200040, China.
Jia
J
Wang
Department of Integrative Medicine, Huashan Hospital, Fudan University, 12 Middle Urumqi Road, Shanghai 200040, China; Institute of Integrated Traditional Chinese and Western Medicine, Fudan University, 12 Middle Urumqi Road, Shanghai 200040, China.
Jinfeng
J
Wu
Department of Integrative Medicine, Huashan Hospital, Fudan University, 12 Middle Urumqi Road, Shanghai 200040, China; Institute of Integrated Traditional Chinese and Western Medicine, Fudan University, 12 Middle Urumqi Road, Shanghai 200040, China.
Lingwen
L
Kong
Department of Integrative Medicine, Huashan Hospital, Fudan University, 12 Middle Urumqi Road, Shanghai 200040, China; Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 501 Haike Road, Shanghai 201203, China; Xinjiang Uygur Medical College, 370 West Beijing Road, Hotan, Xinjiang 848000, China.
Muhammat
M
Nurahmat
Department of Integrative Medicine, Huashan Hospital, Fudan University, 12 Middle Urumqi Road, Shanghai 200040, China; Institute of Integrated Traditional Chinese and Western Medicine, Fudan University, 12 Middle Urumqi Road, Shanghai 200040, China; Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 501 Haike Road, Shanghai 201203, China.
Meixia
M
Chen
Department of Integrative Medicine, Huashan Hospital, Fudan University, 12 Middle Urumqi Road, Shanghai 200040, China; Institute of Integrated Traditional Chinese and Western Medicine, Fudan University, 12 Middle Urumqi Road, Shanghai 200040, China.
Qingli
Q
Luo
Department of Integrative Medicine, Huashan Hospital, Fudan University, 12 Middle Urumqi Road, Shanghai 200040, China; Institute of Integrated Traditional Chinese and Western Medicine, Fudan University, 12 Middle Urumqi Road, Shanghai 200040, China.
Bei
B
Li
Department of Integrative Medicine, Huashan Hospital, Fudan University, 12 Middle Urumqi Road, Shanghai 200040, China; Institute of Integrated Traditional Chinese and Western Medicine, Fudan University, 12 Middle Urumqi Road, Shanghai 200040, China.
Xiao
X
Wu
Department of Integrative Medicine, Huashan Hospital, Fudan University, 12 Middle Urumqi Road, Shanghai 200040, China; Institute of Integrated Traditional Chinese and Western Medicine, Fudan University, 12 Middle Urumqi Road, Shanghai 200040, China. Electronic address: jcdong2004@126.com.
Jingcheng
J
Dong
D000485:Allergens; D000818:Animals; D018927:Anti-Asthmatic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D000893:Anti-Inflammatory Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001249:Asthma / Q000188:drug therapy / Q000209:etiology / Q000276:immunology* / Q000821:virology; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D016207:Cytokines / Q000276:immunology; D004365:Drugs, Chinese Herbal / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D007073:Immunoglobulin E / Q000097:blood; D008168:Lung / Q000187:drug effects / Q000276:immunology / Q000821:virology; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000276:immunology; D008807:Mice, Inbred BALB C; D010047:Ovalbumin; D018357:Respiratory Syncytial Virus Infections / Q000150:complications / Q000188:drug therapy / Q000276:immunology* / Q000821:virology; D012136:Respiratory Syncytial Viruses / Q000502:physiology; D006377:T-Lymphocytes, Helper-Inducer / Q000187:drug effects* / Q000276:immunology; D019562:Viral Load; D014779:Virus Replication
D000485:Allergens; D018927:Anti-Asthmatic Agents; D000893:Anti-Inflammatory Agents; D016207:Cytokines; D004365:Drugs, Chinese Herbal; C000594494:bushenyiqi; D007073:Immunoglobulin E; D010047:Ovalbumin
Acteoside (PubChem CID: 5281800); Allergic airway inflammation; Asthma exacerbation; Baohuoside-I (PubChem CID: 5488822); BuShenYiQi Formula; Calycosin (PubChem CID: 5280448); Calycosin-7-O-β-d-glucoside (PubChem CID: 442813); Dexamethasone (PubChem CID: 5743); Epimedin B (PubChem CID: 5748393); Epimedin C (PubChem CID: 5748394); Helper T lymphocyte; Icariin (PubChem CID: 5318997); Ononin (PubChem CID: 12313740); Respiratory syncytial virus