PMID- 18602364
OWN - NLM
STAT- MEDLINE
DCOM- 20080825
LR  - 20131121
IS  - 1090-2104 (Electronic)
IS  - 0006-291X (Linking)
VI  - 374
IP  - 1
DP  - 2008 Sep 12
TI  - Sphingosine kinase inhibitor suppresses IL-18-induced interferon-gamma production 
      through inhibition of p38 MAPK activation in human NK cells.
PG  - 74-8
LID - 10.1016/j.bbrc.2008.06.091 [doi]
AB  - 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 (S1P), 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-gamma 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.
FAU - Cheon, Soyoung
AU  - Cheon S
AD  - Department of Life Science, Sookmyung Women's University, Hyochangwon-gil 52, 
      Seoul 140-742, Republic of Korea.
FAU - Song, Seok Bean
AU  - Song SB
FAU - Jung, Minkyung
AU  - Jung M
FAU - Park, Yoorim
AU  - Park Y
FAU - Bang, Jung-Wook
AU  - Bang JW
FAU - Kim, Tae Sung
AU  - Kim TS
FAU - Park, Hyunjeong
AU  - Park H
FAU - Kim, Cherl-Hyun
AU  - Kim CH
FAU - Yang, Yool-Hee
AU  - Yang YH
FAU - Bang, Sa Ik
AU  - Bang SI
FAU - Cho, Daeho
AU  - Cho D
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20080703
PL  - United States
TA  - Biochem Biophys Res Commun
JT  - Biochemical and biophysical research communications
JID - 0372516
RN  - 0 (Interleukin-18)
RN  - 0 (Lysophospholipids)
RN  - 0 (Protein Kinase Inhibitors)
RN  - 26993-30-6 (sphingosine 1-phosphate)
RN  - 82115-62-6 (Interferon-gamma)
RN  - EC 2.7.1.- (Phosphotransferases (Alcohol Group Acceptor))
RN  - EC 2.7.1.- (sphingosine kinase)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
RN  - NGZ37HRE42 (Sphingosine)
SB  - IM
MH  - Cell Line
MH  - Enzyme Activation/drug effects
MH  - Humans
MH  - Interferon-gamma/*antagonists & inhibitors/biosynthesis
MH  - Interleukin-18/pharmacology/*physiology
MH  - Killer Cells, Natural/drug effects/*immunology
MH  - Lysophospholipids/biosynthesis
MH  - Phosphorylation/drug effects
MH  - Phosphotransferases (Alcohol Group Acceptor)/antagonists & 
      inhibitors/genetics/*physiology
MH  - Protein Kinase Inhibitors/pharmacology
MH  - Sphingosine/analogs & derivatives/biosynthesis
MH  - p38 Mitogen-Activated Protein Kinases/antagonists & inhibitors
EDAT- 2008/07/08 09:00
MHDA- 2008/08/30 09:00
CRDT- 2008/07/08 09:00
PHST- 2008/06/23 00:00 [received]
PHST- 2008/06/25 00:00 [accepted]
PHST- 2008/07/08 09:00 [pubmed]
PHST- 2008/08/30 09:00 [medline]
PHST- 2008/07/08 09:00 [entrez]
AID - S0006-291X(08)01270-9 [pii]
AID - 10.1016/j.bbrc.2008.06.091 [doi]
PST - ppublish
SO  - Biochem Biophys Res Commun. 2008 Sep 12;374(1):74-8. doi: 
      10.1016/j.bbrc.2008.06.091. Epub 2008 Jul 3.