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The Negative Impact of Triptolide on the Immune Function of Human Natural Killer Cells.

ABSTRACT: Triptolide (TP), a bioactive compound extracted the from traditional Chinese medicine Tripterygium wilfordii Hook F (TwHF), has been shown to be effective in treating several autoimmune diseases, and has suppressive effects in several key immune cells such as dendritic cells, T cells, and macrophages. However, it is unknown whether TP has an impact on natural killer (NK) cells. Here, we report that TP has suppressive effects on human NK cell activity and effector functions. The suppressive effects were observed in human peripheral blood mononuclear cell cultures and purified NK cells from healthy donors, as well as in purified NK cells from patients with rheumatoid arthritis. TP treatment induced downregulation of NK-activating receptor (CD54, CD69) expression and IFN-gamma secretion, in a dose-dependent manner. When exposed to K562 target cells, TP treatment induced inhibition of surface expression of CD107a and IFN-gamma synthesis in NK cells. Furthermore, TP treatment induced activation of inhibitory signaling (SHIP, JNK) and inhibition of MAPK signaling (p38). Thus, our findings demonstrate a previously unknown role for TP in NK cell functional suppression and reveal several key intracellular signaling that can be regulated by TP. Our findings also offer new insight into mechanisms of TP therapeutic treatment in autoimmune disease.

SUBMITTER: Wang N

PROVIDER: S-EPMC10057343 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature

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The Negative Impact of Triptolide on the Immune Function of Human Natural Killer Cells.

Wang Na N Min Xiaoyun X Ma Ning N Zhu Zhuoran Z Cao Bo B Wang Yuan Y Yong Qing Q Huang Jingjin J Li Ke K

Pharmaceuticals (Basel, Switzerland) 20230318 3

Triptolide (TP), a bioactive compound extracted the from traditional Chinese medicine <i>Tripterygium wilfordii</i> Hook F (TwHF), has been shown to be effective in treating several autoimmune diseases, and has suppressive effects in several key immune cells such as dendritic cells, T cells, and macrophages. However, it is unknown whether TP has an impact on natural killer (NK) cells. Here, we report that TP has suppressive effects on human NK cell activity and effector functions. The suppressiv ...[more]

PMID: 36986557

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Project description:Introduction:Ex vivo-expanded natural killer (NK) cells are a potential candidate for cancer immunotherapy based on high cytotoxicity against malignant tumor cells. However, a limited understanding of the migration of activated NK cells toward solid tumors is a critical dilemma in the development of effective and adoptive NK cell-based immunotherapy. Methods:Ex vivo-expanded NK cells from healthy donors were stained with near-infrared fluorophores at different concentrations. NK cell proliferation and cytotoxicity were assessed using a WST-8 assay, while the expression levels of surface molecules were analyzed by flow cytometry. To investigate the biodistribution of NK cells in both normal and tumor-bearing NSG mice, NK cells labeled with ESNF13 were subjected to NIR fluorescence imaging using the Mini-FLARE imaging system. Finally, mice were sacrificed and histopathological tests were performed in resected organs. Results:The signal intensity of ESNF-stained NK cells was long-lasting at 72 h using concentrations as low as 0.04 µM. At a low dose range, ESNF13 did not affect NK cell purity, expression levels of surface receptors, or cytotoxic functions against MDA-MB-231 cancer cells. Ex vivo-expanded NK cells labeled with ESNF13 had a 4-h biodistribution in non-tumor-bearing NSG mice that mainly localized to the lungs immediately after injection and then fully migrated to the kidney after 4 h. In an MDA-MB-231 tumor-bearing NSG mice with extensive metastasis in both lungs, the fluorescence signal was dominant in both lungs and steady at 1, 2, and 4 h post-injection. In a early phase of tumor progression, administered NK cell migrated to the lungs and tumor sites within 30 min post-injection, the signal dominated the tumor site after 1 h, and remained steady at 4 h. Conclusion:Optical imaging with NIR fluorophore ESNF13 is a highly sensitive, applicable, and inexpensive method for the real-time tracking of ex vivo-expanded NK cells both in vitro and in vivo. Administered NK cells had different patterns of NK cell distribution and accumulation to the tumor site according to tumor progression in triple-negative breast cancer xenograft models.

Dataset Information

The Negative Impact of Triptolide on the Immune Function of Human Natural Killer Cells.

Publications

The Negative Impact of Triptolide on the Immune Function of Human Natural Killer Cells.

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