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

doi:10.1016/j.bbrc.2008.06.091

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 journal › Article › peer-review

12 Citations (Scopus)

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-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 language	English
Pages (from-to)	74-78
Number of pages	5
Journal	Biochemical and biophysical research communications
Volume	374
Issue number	1
DOIs	https://doi.org/10.1016/j.bbrc.2008.06.091
Publication status	Published - 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).

Keywords

Interferon-gamma
Interleukin-18
NK cell
Sphingosine kinase
p38MAPK

ASJC Scopus subject areas

Biophysics
Biochemistry
Molecular Biology
Cell Biology

Access to Document

10.1016/j.bbrc.2008.06.091

Cite this

Cheon, S., Song, S. B., Jung, M., Park, Y., Bang, J. W., Kim, T. S., Park, H., Kim, C. H., Yang, Y. H., Bang, S. I., & Cho, D. (2008). Sphingosine kinase inhibitor suppresses IL-18-induced interferon-gamma production through inhibition of p38 MAPK activation in human NK cells. Biochemical and biophysical research communications, 374(1), 74-78. https://doi.org/10.1016/j.bbrc.2008.06.091

Cheon, S, Song, SB, Jung, M, Park, Y, Bang, JW, Kim, TS, Park, H, Kim, CH, Yang, YH, Bang, SI & Cho, D 2008, 'Sphingosine kinase inhibitor suppresses IL-18-induced interferon-gamma production through inhibition of p38 MAPK activation in human NK cells', Biochemical and biophysical research communications, vol. 374, no. 1, pp. 74-78. https://doi.org/10.1016/j.bbrc.2008.06.091

@article{8ccfd998630d4936be3488c42810a25c,

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

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-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.",

keywords = "Interferon-gamma, Interleukin-18, NK cell, Sphingosine kinase, p38MAPK",

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

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{\textquoteright}s Diseases at Sookmyung Women{\textquoteright}s University) of Korea Science and Engineering Foundation (KOSEF) and the Korea Research Foundation (KRF-2004-005-C00012). ",

year = "2008",

month = sep,

day = "12",

doi = "10.1016/j.bbrc.2008.06.091",

language = "English",

volume = "374",

pages = "74--78",

journal = "Biochemical and biophysical research communications",

issn = "0006-291X",

publisher = "Academic Press Inc.",

number = "1",

}

TY - JOUR

T1 - Sphingosine kinase inhibitor suppresses IL-18-induced interferon-gamma production through inhibition of p38 MAPK activation in human NK cells

AU - Cheon, Soyoung

AU - Song, Seok Bean

AU - Jung, Minkyung

AU - Park, Yoorim

AU - Bang, Jung Wook

AU - Kim, Tae Sung

AU - Park, Hyunjeong

AU - Kim, Cherl hyun

AU - Yang, Yool hee

AU - Bang, Sa Ik

AU - Cho, Daeho

N1 - 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).

PY - 2008/9/12

Y1 - 2008/9/12

N2 - 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.

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-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.

KW - Interferon-gamma

KW - Interleukin-18

KW - NK cell

KW - Sphingosine kinase

KW - p38MAPK

UR - http://www.scopus.com/inward/record.url?scp=47749148735&partnerID=8YFLogxK

U2 - 10.1016/j.bbrc.2008.06.091

DO - 10.1016/j.bbrc.2008.06.091

M3 - Article

C2 - 18602364

AN - SCOPUS:47749148735

SN - 0006-291X

VL - 374

SP - 74

EP - 78

JO - Biochemical and biophysical research communications

JF - Biochemical and biophysical research communications

IS - 1

ER -

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

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this