TNF-α production in NKT cell hybridoma is regulated by sphingosine-1-phosphate: Implications for inflammation in atherosclerosis

Shiori Ito, Soichiro Iwaki, Rie Kondo, Masashi Satoh, Kazuya Iwabuchi, Ryunosuke Ohkawa, Yuko Mishima, Yutaka Yatomi, Tomoo Furumoto, Hiroyuki Tsutsui, Satoshi Fujii

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

OBJECTIVES: Natural killer T (NKT) cells are unique T lymphocytes that recognize glycolipid antigen and produce various cytokines. NKT cells accelerate atherosclerosis in mice. Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid and regulates T-lymphocyte trafficking. We aimed to determine the effects of S1P on the production of proinflammatory cytokine, tumor necrosis factor (TNF)-α, in NKT cell hybridomas and mouse NKT cells. MATERIALS AND METHODS: NKT cell hybridomas and sorted mouse NKT cells were stimulated with S1P and α-galactosylceramide (α-GalCer), the major ligand to produce cytokines in NKT cells. TNF-α mRNA expression and protein production were determined by real-time PCR and ELISA, respectively. Cell migration was assayed using chemotaxicell. Plasma S1P was measured using HPLC. RESULTS: Hybridomas expressed S1P receptors, S1P1, S1P2, and S1P4. S1P and α-GalCer increased TNF-α mRNA expression and protein production. S1P enhanced TNF-α induction by α-GalCer. S1P receptor antagonists decreased the TNF-α mRNA expression induced by S1P. FTY720, an immunosuppressive S1P receptor modulator, also decreased the TNF-α mRNA expression. The migration of NKT cell hybridomas was increased by S1P. FTY720 reduced the migration induced by S1P. S1P also increased the TNF-α mRNA expression in mouse NKT cells. Plasma TNF-α levels in patients with high plasma S1P (≥ 500 nmol/l) were higher than those in patients with low S1P (<500 nmol/l). CONCLUSION: S1P binds to S1P receptors in NKT cells and enhances TNF-α production. TNF-α overproduction may induce atherogenic inflammatory responses. S1P may serve as a novel therapeutic target for amelioration of vascular inflammatory diseases.

Original languageEnglish
Pages (from-to)311-320
Number of pages10
JournalCoronary Artery Disease
Volume25
Issue number4
DOIs
Publication statusPublished - Jan 1 2014
Externally publishedYes

Fingerprint

Natural Killer T-Cells
Hybridomas
Atherosclerosis
Tumor Necrosis Factor-alpha
Inflammation
Lysosphingolipid Receptors
Messenger RNA
Cytokines
sphingosine 1-phosphate
Galactosylceramides
T-Lymphocytes
Sphingolipids
Glycolipids
Immunosuppressive Agents
Vascular Diseases
Cell Movement
Real-Time Polymerase Chain Reaction

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine

Cite this

TNF-α production in NKT cell hybridoma is regulated by sphingosine-1-phosphate : Implications for inflammation in atherosclerosis. / Ito, Shiori; Iwaki, Soichiro; Kondo, Rie; Satoh, Masashi; Iwabuchi, Kazuya; Ohkawa, Ryunosuke; Mishima, Yuko; Yatomi, Yutaka; Furumoto, Tomoo; Tsutsui, Hiroyuki; Fujii, Satoshi.

In: Coronary Artery Disease, Vol. 25, No. 4, 01.01.2014, p. 311-320.

Research output: Contribution to journalArticle

Ito, S, Iwaki, S, Kondo, R, Satoh, M, Iwabuchi, K, Ohkawa, R, Mishima, Y, Yatomi, Y, Furumoto, T, Tsutsui, H & Fujii, S 2014, 'TNF-α production in NKT cell hybridoma is regulated by sphingosine-1-phosphate: Implications for inflammation in atherosclerosis', Coronary Artery Disease, vol. 25, no. 4, pp. 311-320. https://doi.org/10.1097/MCA.0000000000000082
Ito, Shiori ; Iwaki, Soichiro ; Kondo, Rie ; Satoh, Masashi ; Iwabuchi, Kazuya ; Ohkawa, Ryunosuke ; Mishima, Yuko ; Yatomi, Yutaka ; Furumoto, Tomoo ; Tsutsui, Hiroyuki ; Fujii, Satoshi. / TNF-α production in NKT cell hybridoma is regulated by sphingosine-1-phosphate : Implications for inflammation in atherosclerosis. In: Coronary Artery Disease. 2014 ; Vol. 25, No. 4. pp. 311-320.
@article{64e1c5ee81f6422fbf2dc15989b942e3,
title = "TNF-α production in NKT cell hybridoma is regulated by sphingosine-1-phosphate: Implications for inflammation in atherosclerosis",
abstract = "OBJECTIVES: Natural killer T (NKT) cells are unique T lymphocytes that recognize glycolipid antigen and produce various cytokines. NKT cells accelerate atherosclerosis in mice. Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid and regulates T-lymphocyte trafficking. We aimed to determine the effects of S1P on the production of proinflammatory cytokine, tumor necrosis factor (TNF)-α, in NKT cell hybridomas and mouse NKT cells. MATERIALS AND METHODS: NKT cell hybridomas and sorted mouse NKT cells were stimulated with S1P and α-galactosylceramide (α-GalCer), the major ligand to produce cytokines in NKT cells. TNF-α mRNA expression and protein production were determined by real-time PCR and ELISA, respectively. Cell migration was assayed using chemotaxicell. Plasma S1P was measured using HPLC. RESULTS: Hybridomas expressed S1P receptors, S1P1, S1P2, and S1P4. S1P and α-GalCer increased TNF-α mRNA expression and protein production. S1P enhanced TNF-α induction by α-GalCer. S1P receptor antagonists decreased the TNF-α mRNA expression induced by S1P. FTY720, an immunosuppressive S1P receptor modulator, also decreased the TNF-α mRNA expression. The migration of NKT cell hybridomas was increased by S1P. FTY720 reduced the migration induced by S1P. S1P also increased the TNF-α mRNA expression in mouse NKT cells. Plasma TNF-α levels in patients with high plasma S1P (≥ 500 nmol/l) were higher than those in patients with low S1P (<500 nmol/l). CONCLUSION: S1P binds to S1P receptors in NKT cells and enhances TNF-α production. TNF-α overproduction may induce atherogenic inflammatory responses. S1P may serve as a novel therapeutic target for amelioration of vascular inflammatory diseases.",
author = "Shiori Ito and Soichiro Iwaki and Rie Kondo and Masashi Satoh and Kazuya Iwabuchi and Ryunosuke Ohkawa and Yuko Mishima and Yutaka Yatomi and Tomoo Furumoto and Hiroyuki Tsutsui and Satoshi Fujii",
year = "2014",
month = "1",
day = "1",
doi = "10.1097/MCA.0000000000000082",
language = "English",
volume = "25",
pages = "311--320",
journal = "Coronary Artery Disease",
issn = "0954-6928",
publisher = "Lippincott Williams and Wilkins",
number = "4",

}

TY - JOUR

T1 - TNF-α production in NKT cell hybridoma is regulated by sphingosine-1-phosphate

T2 - Implications for inflammation in atherosclerosis

AU - Ito, Shiori

AU - Iwaki, Soichiro

AU - Kondo, Rie

AU - Satoh, Masashi

AU - Iwabuchi, Kazuya

AU - Ohkawa, Ryunosuke

AU - Mishima, Yuko

AU - Yatomi, Yutaka

AU - Furumoto, Tomoo

AU - Tsutsui, Hiroyuki

AU - Fujii, Satoshi

PY - 2014/1/1

Y1 - 2014/1/1

N2 - OBJECTIVES: Natural killer T (NKT) cells are unique T lymphocytes that recognize glycolipid antigen and produce various cytokines. NKT cells accelerate atherosclerosis in mice. Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid and regulates T-lymphocyte trafficking. We aimed to determine the effects of S1P on the production of proinflammatory cytokine, tumor necrosis factor (TNF)-α, in NKT cell hybridomas and mouse NKT cells. MATERIALS AND METHODS: NKT cell hybridomas and sorted mouse NKT cells were stimulated with S1P and α-galactosylceramide (α-GalCer), the major ligand to produce cytokines in NKT cells. TNF-α mRNA expression and protein production were determined by real-time PCR and ELISA, respectively. Cell migration was assayed using chemotaxicell. Plasma S1P was measured using HPLC. RESULTS: Hybridomas expressed S1P receptors, S1P1, S1P2, and S1P4. S1P and α-GalCer increased TNF-α mRNA expression and protein production. S1P enhanced TNF-α induction by α-GalCer. S1P receptor antagonists decreased the TNF-α mRNA expression induced by S1P. FTY720, an immunosuppressive S1P receptor modulator, also decreased the TNF-α mRNA expression. The migration of NKT cell hybridomas was increased by S1P. FTY720 reduced the migration induced by S1P. S1P also increased the TNF-α mRNA expression in mouse NKT cells. Plasma TNF-α levels in patients with high plasma S1P (≥ 500 nmol/l) were higher than those in patients with low S1P (<500 nmol/l). CONCLUSION: S1P binds to S1P receptors in NKT cells and enhances TNF-α production. TNF-α overproduction may induce atherogenic inflammatory responses. S1P may serve as a novel therapeutic target for amelioration of vascular inflammatory diseases.

AB - OBJECTIVES: Natural killer T (NKT) cells are unique T lymphocytes that recognize glycolipid antigen and produce various cytokines. NKT cells accelerate atherosclerosis in mice. Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid and regulates T-lymphocyte trafficking. We aimed to determine the effects of S1P on the production of proinflammatory cytokine, tumor necrosis factor (TNF)-α, in NKT cell hybridomas and mouse NKT cells. MATERIALS AND METHODS: NKT cell hybridomas and sorted mouse NKT cells were stimulated with S1P and α-galactosylceramide (α-GalCer), the major ligand to produce cytokines in NKT cells. TNF-α mRNA expression and protein production were determined by real-time PCR and ELISA, respectively. Cell migration was assayed using chemotaxicell. Plasma S1P was measured using HPLC. RESULTS: Hybridomas expressed S1P receptors, S1P1, S1P2, and S1P4. S1P and α-GalCer increased TNF-α mRNA expression and protein production. S1P enhanced TNF-α induction by α-GalCer. S1P receptor antagonists decreased the TNF-α mRNA expression induced by S1P. FTY720, an immunosuppressive S1P receptor modulator, also decreased the TNF-α mRNA expression. The migration of NKT cell hybridomas was increased by S1P. FTY720 reduced the migration induced by S1P. S1P also increased the TNF-α mRNA expression in mouse NKT cells. Plasma TNF-α levels in patients with high plasma S1P (≥ 500 nmol/l) were higher than those in patients with low S1P (<500 nmol/l). CONCLUSION: S1P binds to S1P receptors in NKT cells and enhances TNF-α production. TNF-α overproduction may induce atherogenic inflammatory responses. S1P may serve as a novel therapeutic target for amelioration of vascular inflammatory diseases.

UR - http://www.scopus.com/inward/record.url?scp=84899949700&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84899949700&partnerID=8YFLogxK

U2 - 10.1097/MCA.0000000000000082

DO - 10.1097/MCA.0000000000000082

M3 - Article

C2 - 24448174

AN - SCOPUS:84899949700

VL - 25

SP - 311

EP - 320

JO - Coronary Artery Disease

JF - Coronary Artery Disease

SN - 0954-6928

IS - 4

ER -