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Adiponectin Is a Negative Regulator of NK Cell Cytotoxicity¹

Kun-yong Kim^*, Jae Kwang Kim^*, Seung Hyun Han, Jong-Seok Lim^*, Keun Il Kim^*, Dae Ho Cho^*, Myeong-Sok Lee^*, Jeong-Hyung Lee, Do-Young Yoon, Suk Ran Yoon, Jin Woong Chung, Inpyo Choi, Eunjoon Kim^¶ and Young Yang^2,*

^* Laboratory of Molecular and Cellular Biology, Department of Life Science, Sookmyung Women’s University, Seoul, Korea; Department of Oromaxillofacial Infection Immunity and Dental Research Institute, School of Dentistry, Seoul National University, Seoul, Korea; Korea Research Institute of Bioscience and Biotechnology, Daejon, Korea; Department of Bioscience and Biotechnology, Konkuk University, Seoul, Korea; and ^¶ Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejon, Korea

NK cells are a key component of innate immune systems, and their activity is regulated by cytokines and hormones. Adiponectin, which is secreted from white adipose tissues, plays important roles in various diseases, including hypertension, cardiovascular diseases, inflammatory disorders, and cancer. In this study the effect of adiponectin on NK cell activity was investigated. Adiponectin was found to suppress the IL-2-enhanced cytotoxic activity of NK cells without affecting basal NK cell cytotoxicity and to inhibit IL-2-induced NF-B activation via activation of the AMP-activated protein kinase, indicating that it suppresses IL-2-enhanced NK cell cytotoxicity through the AMP-activated protein kinase-mediated inhibition of NF-B activation. IFN- enhances NK cell cytotoxicity by causing an increase in the levels of expression of TRAIL and Fas ligand. The production of IFN-, one of the NF-B target genes in NK cells, was also found to be suppressed by adiponectin, accompanied by the subsequent down-regulation of IFN--inducible TRAIL and Fas ligand expression. These results clearly demonstrate that adiponectin is a potent negative regulator of IL-2-induced NK cell activation and thus may act as an in vivo regulator of anti-inflammatory functions.

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