Activation of the human natural killer cells NK-92 with a lymphocyte-derived cytokine-rich supernatant.

Voutsas, Ioannis F.; Samara, Pinelopi; Tsiatas, Marinos; Skopeliti, Margarita; Fortis, Sotirios P.; Bamias, Aristotelis; Georgaki, Sylvianna; Tsitsilonis, Ourania E.

doi:10.1200/jco.2014.32.15_suppl.3108

Cited by 1 publication

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“…They are effector cells of both innate and adaptive immune responses and kill tumor cells and virally infected cells. NK cells are activated in response to interferon-γ (IFN-γ) or macrophage-derived cytokines, such as interleukin (IL)-2, IL-12, IL-15, IL-18, and C-C motif chemokine ligand 5 (CCL5) (Kang et al, 2014;Voutsas et al, 2014;H. Wang et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

“…They are effector cells of both innate and adaptive immune responses and kill tumor cells and virally infected cells. NK cells are activated in response to interferon‐γ (IFN‐γ) or macrophage‐derived cytokines, such as interleukin (IL)‐2, IL‐12, IL‐15, IL‐18, and C‐C motif chemokine ligand 5 (CCL5) (Kang et al., 2014; Voutsas et al., 2014; H. Wang et al., 2018). Upon activation, NK cells not only release IFN‐γ (Cui et al., 2019) to directly recognize and kill target cells, but also activate cytotoxic T cells and B cells through cytokine secretion to augment the immune response (Michel et al., 2012; Pallmer & Oxenius, 2016; Schuster et al., 2016).…”

Section: Introductionmentioning

confidence: 99%

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Curcuma longa enhances IFN‐γ secretion by natural killer cells through cytokines secreted from macrophages

Seo¹,

Ahn²,

Jin³

et al. 2021

Journal of Food Science

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Interferon-γ (IFN-γ) regulates the human immune system. To study the interaction between macrophages and natural killer (NK) cells, we established a THP-1 macrophage-conditioned media. Among the 58 natural plant extracts tested, Curcuma longa exerted the strongest IFN-γ-enhancing effect in NK-92 cells through THP-1 macrophages. C. longa extract (CLE) enhanced IFN-γ secretion 2.3-and 4.2-fold at 50 and 100 µg/ml, respectively. Therefore, we evaluated its IFN-γ-enhancing effect in vitro. Although NK-92 cells did not produce IFN-γ following treatment with C. longa, enhanced IFN-γ secretion was observed after treatment with THP-1 macrophage-conditioned media. We hypothesized that the cytokines secreted by the CLE-treated THP-1 macrophages are responsible for stimulating NK-92 cells. Cytokine array results show upregulation of cytokines, including MIP-1α, CXCL-1, IL-1β, PAI-1, and TNF-α, in CLEtreated THP-1 macrophages. To determine the cytokines responsible for augmenting IFN-γ secretion, NK-92 cells were stimulated with MIP-1α, CXCL-1, IL-1β, or PAI-1. Enzyme-linked immunosorbent assay results show that all cytokines induced IFN-γ production, although the dose response was somewhat varied. High-performance liquid chromatography analysis of CLE revealed the concentrations of three active curcuminoids, curcumin, demethoxycurcumin, and bisdemethoxycurcumin, as 6.70%, 1.00%, and 0.95%, respectively. Their mixture (with concentrations comparable to their occurrence in CLE) exerted an effect similar to that of the whole CLE. Our findings reveal that CLE indirectly stimulated NK-92 cells to secrete IFN-γ, which is mediated by cytokines produced from THP-1 macrophages. Further, we identified three curcuminoids partly responsible for this IFN-γ-enhancing effect. Therefore, C. longa can be used as a functional food ingredient owing to its immune-boosting ability. Practical Application: This study demonstrates that CLE stimulates THP-1 macrophages to secrete cytokines, which can in turn stimulate IFN-γ production by NK-92 cells. A mixture of three curcuminoids present in the extract exerted effects similar to whole CLE, demonstrating that the curcuminoids are partly responsible for the IFN-γ-enhancing effect of C. longa. Since IFN-γ is a key regulator of human immune system, these results suggest the potential use of C. longa as an immune-boosting functional food ingredient.

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Section: Introductionmentioning

confidence: 99%