Adiponectin is a negative regulator of NK cell cytotoxicity.
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-kappaB 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-kappaB activation. IFN-gamma enhances NK cell cytotoxicity by causing an increase in the levels of expression of TRAIL and Fas ligand. The production of IFN-gamma, one of the NF-kappaB target genes in NK cells, was also found to be suppressed by adiponectin, accompanied by the subsequent down-regulation of IFN-gamma-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.
Kim
Kun-Yong
KY
Laboratory of Molecular and Cellular Biology, Department of Life Science, Sookmyung Women's University, Seoul 140-742, Korea.
Kim
Jae Kwang
JK
Han
Seung Hyun
SH
Lim
Jong-Seok
JS
Kim
Keun Il
KI
Cho
Dae Ho
DH
Lee
Myeong-Sok
MS
Lee
Jeong-Hyung
JH
Yoon
Do-Young
DY
Yoon
Suk Ran
SR
Chung
Jin Woong
JW
Choi
Inpyo
I
Kim
Eunjoon
E
Yang
Young
Y