Höfundar:
Jessica Webb, Kirstine Nolling Jensen, Ingibjorg Hardardottir, Jona Freysdottir
Introduction: Improper resolution of inflammation is involved in many disease pathologies, including that of arthritis, cancer, and inflammatory bowel disease. Natural killer (NK) cells have long been implicated in the promotion of inflammation through release of pro-inflammatory cytokines and cytotoxic molecules. More recently, they have been implicated to play an important role in resolution of inflammation. The aim of this study was to determine whether human NK cells in culture can be induced to express a resolution of inflammation phenotype.
Methods: NK cells were isolated from buffy coat, cultured, and stimulated with IL-10, IL-15, TGFβ, and RvE1 (resolution cocktail, RES); IL-2, IL-12, and IL-15 (inflammatory cocktail, INF); or IL-15 alone (control, C). Concentrations of the specialized pro-resolving mediators (SPMs) lipoxin A4 and annexin A1 and the pro-inflammatory cytokine IFN-γ in the supernatant were determined by SimpleWestern and ELISA and NK cell expression of surface molecules by flow cytometry.
Results: NK cells cultured with RES had higher concentrations of lipoxin A4 in their supernatants than NK cells cultured with INF. They also expressed more annexin A1 than NK cells cultured with INF or C. NK cells cultured with RES secreted less IFN-γ and expressed less of the cytotoxicity-linked adhesion molecule DNAM-1 than NK cells cultured with INF.
Conclusions: Culturing NK cells with RES increased their production of SPMs and decreased their production of pro-inflammatory and cytotoxicity-linked molecules, indicating that NK cells may be induced to express a resolution of inflammation phenotype in culture.