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

Soyoung Cheon, Seok Bean Song, Minkyung Jung, Yoorim Park, Jung Wook Bang, Tae Sung Kim, Hyunjeong Park, Cherl hyun Kim, Yool hee Yang, Sa Ik Bang, Daeho Cho

Research output: Contribution to journalArticlepeer-review

11 Citations (Scopus)


Natural killer (NK) cells play an important role in the innate immune response. Interleukin-18 (IL-18) is a well-known interferon-gamma (IFN-γ 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-γ production, we measured IL-18-induced IFN-γ production after pre-treatment with SPHK inhibitor (SKI) in NK-92MI cells. We found that IL-18-induced IFN-γ expression was blocked by SKI pre-treatment in both mRNA and protein levels. In addition, the increased IFN-γ 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-γ 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-γ production in human primary NK cells. In conclusion, SPHK activation is an essential factor for IL-18-induced IFN-γ production via p38 MAPK.

Original languageEnglish
Pages (from-to)74-78
Number of pages5
JournalBiochemical and biophysical research communications
Issue number1
Publication statusPublished - 2008 Sept 12

Bibliographical note

Funding Information:
This work was supported by a grant of the Korea Health 21 R&D Project, Ministry of Health & Welfare, Republic of Korea (A050569) and the SRC program (Research Center for Women’s Diseases at Sookmyung Women’s University) of Korea Science and Engineering Foundation (KOSEF) and the Korea Research Foundation (KRF-2004-005-C00012).


  • Interferon-gamma
  • Interleukin-18
  • NK cell
  • Sphingosine kinase
  • p38MAPK

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology


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