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Curcuma longa enhances IFN‐γ secretion by natural killer cells through cytokines secreted from macrophages
Author(s) -
Seo Sang Gwon,
Ahn Young Je,
Jin Mu Hyun,
Kang Nae Gyu,
Cho Ho Song
Publication year - 2021
Publication title -
journal of food science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.772
H-Index - 150
eISSN - 1750-3841
pISSN - 0022-1147
DOI - 10.1111/1750-3841.15821
Subject(s) - curcuma , secretion , macrophage , cytokine , immune system , proinflammatory cytokine , thp1 cell line , tumor necrosis factor alpha , biology , interferon , immunology , interferon gamma , in vitro , curcumin , chemistry , cell culture , inflammation , pharmacology , biochemistry , botany , genetics
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 CLE‐treated 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.