Atractylodin ameliorates ovalbumin‑induced asthma in a mouse model and exerts immunomodulatory effects on Th2 immunity and dendritic cell function

Lin,Yu‑Chao; Yang,Ching‑Chieh; Lin,Ching‑Hsiung; Hsia,Te‑Chun; Chao,Wen‑Cheng; Lin,Chi‑Chien

doi:10.3892/mmr.2020.11569

Atractylodin ameliorates ovalbumin‑induced asthma in a mouse model and exerts immunomodulatory effects on Th2 immunity and dendritic cell function

Authors:
- Yu‑Chao Lin
- Ching‑Chieh Yang
- Ching‑Hsiung Lin
- Te‑Chun Hsia
- Wen‑Cheng Chao
- Chi‑Chien Lin
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Affiliations: Graduate Institute of Clinical Medical Science, Department of Medicine, China Medical University, Taichung 40402, Taiwan, R.O.C., Department of Radiation Oncology, Chi‑Mei Hospital, Tainan 71004, Taiwan, R.O.C., Department of Internal Medicine, Division of Chest Medicine, Changhua Christian Hospital, Changhua 50006, Taiwan, R.O.C., Department of Critical Care Medicine, Taichung Veterans General Hospital, Taichung 40705, Taiwan, R.O.C., Institute of Biomedical Science, Department of Life Sciences, The iEGG and Animal Biotechnology Center, National Chung‑Hsing University, Taichung 40227, Taiwan, R.O.C.
Published online on: October 7, 2020 https://doi.org/10.3892/mmr.2020.11569
Pages: 4909-4918

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Abstract

Asthma is a leading allergic disease worldwide, demonstrating an ever‑increasing prevalence over the past two decades. Asthma is characterized by allergen‑associated airway hyperresponsiveness (AHR) that primarily results from T helper 2 (Th2) cell inflammation, in which dendritic cells (DCs) serve an important role in determining T cell development after encountering an antigen. Atractylodin (ATL), a polyethene alkyne extracted from Atractylodis rhizoma (also known as Cangzhu), has proven effective in treating digestive disorders, rheumatic disease and influenza. In addition, ATL was discovered to alleviate mouse collagen‑induced arthritis via regulating DC maturation. The present study aimed to investigate the effect of ATL on asthma given that DCs serve an essential role in Th2‑mediated inflammation in asthma. Mouse model of asthma was induced by ovalbumin (OVA). OVA‑induced airway hyperresponsiveness (AHR) and inflammatory cells in bronchoalveolar lavage fluid (BALF) were detected. The production of IgE and IgG1 in serum and cytokines in BALF were detected by ELISA. The effects of ATL on dendritic cells maturation and T cell expansion were detected by flow cytometry analysis and 3H‑thymidine incorporation. Using a model of OVA‑induced asthma, it was demonstrated that ATL ameliorated AHR and decreased the levels of IL‑4, IL‑5 and IL‑13 in bronchoalveolar lavage fluid (BALF), and OVA‑specific IgE and IgG1 in the serum. OVA‑stimulated splenocytes were used to demonstrated that ATL decreased cell expansion and the production of IL‑4, IL‑5 and IL‑13 in the culture medium. In order to determine the cellular mechanism of ATL in asthma, splenic DCs were isolated and it was subsequently observed that ATL downregulated the expression levels of CD40 and CD80. Furthermore, OVA‑stimulated CD4+ T cells were co‑cultured with splenic DCs, which revealed that ATL‑treated splenic DCs led to impaired cellular proliferation and the production of IL‑4, IL‑5 and IL‑13 in OVA‑stimulated T cells. In conclusion, these results indicated that ATL may suppress antigen‑specific Th2 responses in an OVA‑induced allergic asthma model via regulating DCs. Therefore, ATL may exhibit therapeutic potential in the management of asthma and other allergic diseases presenting with Th2 inflammation.

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