Role of interleukin-18 in human natural killer cell is associated with interleukin-2 |
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| Affiliation: | 1. Laboratory of Molecular Virology, Center for Biologics Evaluation and Research, Food and Drug Administration, 1401 Rockville Pike, Rockville, MD 20892, USA;2. Department of Life Science, Northwestern Polytechnical University, 127 Youyi Xilu, Xi’an, Shaanxi 710072, China;3. Department of Microbiology, The Fourth Military Medical University, 17 Changle Xilu, Xi’an, Shaanxi 710032, China;1. Laboratory of Molecular and Tumor Immunology, Robert W. Franz Cancer Center, Earle A. Chiles Research Institute, Providence Cancer Institute, Providence Portland Medical Center, Portland, OR, USA;2. Oregon Health & Science University, Portland, OR, USA;3. UbiVac, Portland, OR, USA;4. Boehringer Ingelheim Pharmaceuticals, Inc., 900 Ridgebury Road, Ridgefield, CT 06877-0368, USA;1. Department of Molecular Science and Technology, Ajou University, Suwon 443-749, Republic of Korea;2. School of Civil, Environmental and Architectural Engineering, Korea University, Seoul 136-713, Republic of Korea;3. Department of Chemical Engineering, Kwangwoon University, Seoul 139-701, Republic of Korea;4. College of Veterinary Medicine, Seoul National University, Seoul 151-742, Republic of Korea;1. Research Scholar, Department of Anatomy, All India Institute of Medical Sciences, New Delhi, India;2. Professor, Department of Anatomy, Hamdard Institute of Medical Sciences and Research (HIMSR), Jamia Hamdard, New Delhi, India;3. Professor, Department of Anatomy, All India Institute of Medical Sciences, New Delhi, India;1. Department of Cell Biology and Neuroscience, Rutgers University, Piscataway, NJ 08854, USA;2. A-T Clinic, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA;3. Department of Genetics, Rutgers University, Piscataway, NJ 08854, USA;4. Human Genetics Institute of New Jersey, Piscataway, NJ 08854, USA |
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| Abstract: | ![]()
Human natural killer (NK) cells constitute an important cellular component of innate immunity, capable of killing infected and transformed cells. The proliferation and activation of NK cells are regulated by various cytokines. Interleukin-18 (IL-18) promotes NK cell activation; however, whether the effects of IL-18 on NK cell are associated with other cytokines is still unknown. In this study, we observed that IL-18 induced NK cell apoptosis and inhibited NK cell expansion in the presence of low concentrations of interleukin-2 (IL-2), while high concentrations of IL-2 overcame these effects of IL-18, and high concentrations of IL-2 promoted the stimulatory activity of IL-18 on NK cells. At a low concentration of IL-2, IL-18 induced NK cell apoptosis in part through activation of the FasL/Fas- and TNFα/TNFR-mediated death receptor signaling by enhancing FasL expression and inhibiting c-FLIPlong expression. However, high concentrations of IL-2 strongly blocked IL-18-induced NK cell apoptosis through alleviating IL-18-induced FasL expression and activation of Fas-mediated death signaling and increasing anti-apoptosis molecule (Bcl-XL). These results reveal that the effects of IL-18 on human NK cell are associated with IL-2 concentration and suggest the importance of IL-2 level in cytokine immunotherapy. |
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