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Osthole treatment ameliorates Th2-mediated allergic asthma and exerts immunomodulatory effects on dendritic cell maturation and function

Cellular & Molecular Immunology volume 14, pages 935–947 (2017)Cite this article

Abstract

Osthole, an active component of Chinese herbal medicines, reportedly possesses various pharmacological properties and has potential therapeutic applications. This study explored the anti-allergic effects of osthole in asthmatic mice and investigated the immunomodulatory actions of osthole on dendritic cells (DCs) and T cells. Herein, we show that oral administration of osthole to BALB/c mice after ovalbumin (OVA) sensitization ameliorated all of the cardinal features of T helper 2 (Th2)-mediated allergic asthma; namely, the production of OVA-specific immunoglobulin E, airway hyperresponsiveness, airway inflammation and the production of Th2-type cytokines including interleukin (IL)-4, IL-5 and IL-13. Surprisingly, IL-10 production was not inhibited and was even enhanced by osthole treatment. We observed a significant increase in the percentages of IL-10-producing DCs and forkhead box P3-positive regulatory T (Treg) cells in osthole-treated asthmatic mice. Additionally, in vitro analyses revealed that osthole-treated bone-marrow-derived DCs had a partial maturation phenotype, secreting large amounts of IL-10 and low levels of proinflammatory cytokines, such as IL-12, IL-6 and tumor necrosis factor-α, and displaying reduced levels of MHC class II surface molecules. These DCs displayed immunosuppressive capacity by directly inhibiting effector T-cell responses or inducing Treg cells. In addition, osthole directly inhibited the activated CD4+ T-cell proliferation and Th1/Th2-type cytokine production in this system. Collectively, these results suggest that DCs and T cells are potential target cells responsible for the action of osthole against allergic asthma.

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Acknowledgements

This study was supported by research grants from the Ministry of Science and Technology, Taiwan (MOST 103-2320-B-038-032-MY3) and Wan Fang Hospital, Taipei, Taiwan (104TMU-WFH-14).

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Author notes

  1. Chen-Yuan Chiang and Chen-Chen Lee: These authors contributed equally to this work.

Authors and Affiliations

  1. Division of Pulmonary Medicine, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, 11031, Taiwan, China

    Chen-Yuan Chiang

  2. Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, 11031, Taiwan, China

    Chen-Yuan Chiang

  3. Department of Microbiology and Immunology, School of Medicine, College of Medicine, China Medical University, Taichung, 40402, Taiwan, China

    Chen-Chen Lee

  4. Department of Parasitology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, 11031, Taiwan, China

    Chia-Kwung Fan

  5. Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, 11031, Taiwan, China

    Huei-Mei Huang

  6. Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, 10048, Taiwan, China

    Bor-Luen Chiang

  7. Department of Microbiology and Immunology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, 11031, Taiwan, China

    Yueh-Lun Lee

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Correspondence to Yueh-Lun Lee.

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Chiang, CY., Lee, CC., Fan, CK. et al. Osthole treatment ameliorates Th2-mediated allergic asthma and exerts immunomodulatory effects on dendritic cell maturation and function. Cell Mol Immunol 14, 935–947 (2017). https://doi.org/10.1038/cmi.2017.71

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