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Sphingosine kinase inhibitor suppresses IL-18-induced interferon-gamma production through inhibition of p38 MAPK activation in human NK cells

Authors
Cheon, SoyoungSong, Seok BeanJung, MinkyungPark, YoorimBang, Jung-WookKim, Tae SungPark, HyunjeongKim, Cher-hyunYang, Yool-heeBang, Sa IkCho, Daeho
Issue Date
12-Sep-2008
Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
Keywords
sphingosine kinase; interleukin-18; interferon-gamma; p38MAPK; NK cell
Citation
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, v.374, no.1, pp 74 - 78
Pages
5
Journal Title
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
Volume
374
Number
1
Start Page
74
End Page
78
URI
https://scholarworks.sookmyung.ac.kr/handle/2020.sw.sookmyung/14179
DOI
10.1016/j.bbrc.2008.06.091
ISSN
0006-291X
1090-2104
Abstract
Natural killer (NK) cells play an important role in the innate immune response. Interleukin-18 (IL-18) is a well-known interferon-gamma (IFN-gamma inducing factor, which stimulates immune response in NK and T cells. Sphingosine kinase (SPHK) catalyzes the formation of sphingosine 1-phosphate (SI P), which acts as a second messenger to function as an anti-apoptotic factor and proliferation stimulator of immune cells. In this study, to elucidate whether SPHK is involved in IL-18-induced IFN-gamma production, we measured IL-18-induced IFN-gamma production after pre-treatment with SPHK inhibitor (SKI) in NK-92MI cells. We found that IL-18-induced IFN-gamma expression was blocked by SKI pre-treatment in both mRNA and protein levels. in addition, the increased IFN-1 production by stimulation with IL-18 is mediated through both SPHK and p38 MAPK. To determine the upstream signals of SKI and p38 MAPK in IL-18-induced IFN-gamma production, phosphorylation levels of p38 MAPK was measured after SKI pre-treatment. As a result, inhibition of SPHK by SKI blocked phosphorylation of p38 MAPK, showing that SPHK activation by IL-18 is an upstream signal of p38 MAPK activation. Inhibition of SPHK by SKI also inhibited IL-18-induced IFN-gamma production in human primary NK cells. In conclusion, SPHK activation is an essential factor for IL-18-induced IFN-gamma production via p38 MAPK. (C) 2008 Elsevier Inc. All rights reserved.
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