التفاصيل البيبلوغرافية
| العنوان: |
Unexpected mechanism of colitis amelioration by artesunate, a natural product from Artemisia annua L. |
| المؤلفون: |
Sun, Weili, Han, Xiao, Wu, Siyuan, Wu, Jianghong, Yang, Chuanhua, Li, Xuhang |
| المصدر: |
Inflammopharmacology; Aug2020, Vol. 28 Issue 4, p851-868, 18p |
| مصطلحات موضوعية: |
ARTEMISININ derivatives, DENDRITIC cells, ARTEMISIA annua, COLITIS, NATURAL products, APOPTOSIS, INFLAMMATORY bowel diseases |
| مستخلص: |
Background: Artemisinin and its derivatives are known to exert immunosuppressive effects through modulating adaptive immunity. We investigated a novel role of artesunate in regulating innate immunity, including both macrophages (MΦ) and dendritic cells (DCs), which are known to involve in DSS-induced colitis. Methods: Effects of artesunate on innate immunity were extensively evaluated, both in vivo using DSS-colitis model with WT and T cell-deficient RAG mice (RAG−/−) and in vitro using cell culture models, including in-depth analyses of MΦ/DC apoptosis and cytokine expression by flow cytometry, Western blot, or immunohistology. Results: Unexpectedly, artesunate significantly ameliorated the DSS colitis of both WT and RAG1−/− mice with similar potency, suggesting a mechanism that involves primarily innate rather than adaptive immunity. In vivo mechanistic studies revealed that artesunate markedly induced apoptosis of lamina propria MΦs and DCs and suppressed mucosal TNF-α and IL-12p70 in DSS-colitis. In vitro, artesunate potently induced a dose- and time-dependent apoptosis of murine bone marrow-derived DCs and human THP-1 MΦs, through the caspases-9-mediated intrinsic pathway. Artesunate significantly decreased the secretion of IL-12p40/70 by DCs and TNF-α by MΦs. Furthermore, a combination of artesunate with an immunomodulator (methotrexate/triptolide/azathioprine) exhibited superior potency in promoting apoptosis of MΦs than any individual drug alone. Conclusions: The immunomodulatory mechanism of artesunate in colitis involves a novel and potent induction of the intrinsic apoptosis pathway of proliferating MΦs and DCs and suppression of IL-12 and TNF-α. Artemisinin and its derivatives are promising new therapeutic alternatives for IBD, either alone or in combination with other immunomodulators. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
Complementary Index |
