Se-methylselenocysteine inhibits lipopolysaccharide-induced NF-κB activation and iNOS induction in RAW 264.7 murine macrophages

Min Hsiung Pan, Huei Mei Hong, Chih Li Lin, Ai Zhi Jhang, Jie Heng Tsai, Vladimir Badmaev, Kalyanam Nagabhushanam, Chi-Tang Ho, Wei Jen Chen

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Scope: Se-methyl-L-selenocysteine (MSC), a naturally occurring organoselenium compound, has shown cancer chemopreventive activity against several types of cancer. Herein, the effect of MSC on the inflammatory response in lipopolysaccharide (LPS)-activated murine RAW 264.7 macrophage cells was investigated. Methods and results: The present results demonstrated that MSC markedly inhibited LPS-induced production of NO in a dose-dependent pattern with decreased mRNA and protein levels of inducible nitric oxide synthase (iNOS). MSC also reduced nuclear translocation of p65 and p50 subunits of nuclear factor-κB (NF-κB), a critical transcription factor necessary for iNOS expression, accompanied with downregulation of LPS-triggered NF-κB-dependent gene expression evaluating by a luciferase reporter. Inhibition of nuclear translocation by MSC might result from the prevention of the inhibitor of NF-κB from phosphorylation and consequent degradation via suppression inhibition of phosphorylation of IκB kinase α/β. Exploring the action mechanism involved, MSC can reduce the phosphorylation/activation of mitogen-activated protein kinases (MAPKs) related to NF-κB activation induced by LPS, including p38 MAPK and c-Jun N-terminal kinase in RAW 264.7 cells. Conclusion: MSC might contribute to the potent anti-inflammatory effect in LPS-activated RAW 264.7 cells via downregulation of NF-κB activation and iNOS expression, suggesting that MSC may be considered as a therapeutic candidate for chronic inflammatory diseases.

Original languageEnglish (US)
Pages (from-to)723-732
Number of pages10
JournalMolecular Nutrition and Food Research
Volume55
Issue number5
DOIs
StatePublished - May 1 2011

Fingerprint

selenocysteine
Nitric Oxide Synthase Type II
lipopolysaccharides
Lipopolysaccharides
macrophages
Macrophages
mice
mitogen-activated protein kinase
phosphorylation
Phosphorylation
Organoselenium Compounds
Down-Regulation
neoplasms
cells
luciferase
methylselenocysteine
inducible nitric oxide synthase
selenomethylselenocysteine
JNK Mitogen-Activated Protein Kinases
anti-inflammatory activity

All Science Journal Classification (ASJC) codes

  • Food Science
  • Biotechnology

Keywords

  • C-Jun N-terminal kinase (JNK)
  • Inducible NO synthesis (iNOS)
  • NF-κB
  • P38 mitogen-activated protein kinase (p38 MAPK)
  • Se-methyl-L-selenocysteine (MSC)

Cite this

Pan, Min Hsiung ; Hong, Huei Mei ; Lin, Chih Li ; Jhang, Ai Zhi ; Tsai, Jie Heng ; Badmaev, Vladimir ; Nagabhushanam, Kalyanam ; Ho, Chi-Tang ; Chen, Wei Jen. / Se-methylselenocysteine inhibits lipopolysaccharide-induced NF-κB activation and iNOS induction in RAW 264.7 murine macrophages. In: Molecular Nutrition and Food Research. 2011 ; Vol. 55, No. 5. pp. 723-732.
@article{bf8d29e627d5484584a0eb4c4b8835d2,
title = "Se-methylselenocysteine inhibits lipopolysaccharide-induced NF-κB activation and iNOS induction in RAW 264.7 murine macrophages",
abstract = "Scope: Se-methyl-L-selenocysteine (MSC), a naturally occurring organoselenium compound, has shown cancer chemopreventive activity against several types of cancer. Herein, the effect of MSC on the inflammatory response in lipopolysaccharide (LPS)-activated murine RAW 264.7 macrophage cells was investigated. Methods and results: The present results demonstrated that MSC markedly inhibited LPS-induced production of NO in a dose-dependent pattern with decreased mRNA and protein levels of inducible nitric oxide synthase (iNOS). MSC also reduced nuclear translocation of p65 and p50 subunits of nuclear factor-κB (NF-κB), a critical transcription factor necessary for iNOS expression, accompanied with downregulation of LPS-triggered NF-κB-dependent gene expression evaluating by a luciferase reporter. Inhibition of nuclear translocation by MSC might result from the prevention of the inhibitor of NF-κB from phosphorylation and consequent degradation via suppression inhibition of phosphorylation of IκB kinase α/β. Exploring the action mechanism involved, MSC can reduce the phosphorylation/activation of mitogen-activated protein kinases (MAPKs) related to NF-κB activation induced by LPS, including p38 MAPK and c-Jun N-terminal kinase in RAW 264.7 cells. Conclusion: MSC might contribute to the potent anti-inflammatory effect in LPS-activated RAW 264.7 cells via downregulation of NF-κB activation and iNOS expression, suggesting that MSC may be considered as a therapeutic candidate for chronic inflammatory diseases.",
keywords = "C-Jun N-terminal kinase (JNK), Inducible NO synthesis (iNOS), NF-κB, P38 mitogen-activated protein kinase (p38 MAPK), Se-methyl-L-selenocysteine (MSC)",
author = "Pan, {Min Hsiung} and Hong, {Huei Mei} and Lin, {Chih Li} and Jhang, {Ai Zhi} and Tsai, {Jie Heng} and Vladimir Badmaev and Kalyanam Nagabhushanam and Chi-Tang Ho and Chen, {Wei Jen}",
year = "2011",
month = "5",
day = "1",
doi = "https://doi.org/10.1002/mnfr.201000481",
language = "English (US)",
volume = "55",
pages = "723--732",
journal = "Molecular Nutrition and Food Research",
issn = "1613-4125",
publisher = "Wiley-VCH Verlag",
number = "5",

}

Se-methylselenocysteine inhibits lipopolysaccharide-induced NF-κB activation and iNOS induction in RAW 264.7 murine macrophages. / Pan, Min Hsiung; Hong, Huei Mei; Lin, Chih Li; Jhang, Ai Zhi; Tsai, Jie Heng; Badmaev, Vladimir; Nagabhushanam, Kalyanam; Ho, Chi-Tang; Chen, Wei Jen.

In: Molecular Nutrition and Food Research, Vol. 55, No. 5, 01.05.2011, p. 723-732.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Se-methylselenocysteine inhibits lipopolysaccharide-induced NF-κB activation and iNOS induction in RAW 264.7 murine macrophages

AU - Pan, Min Hsiung

AU - Hong, Huei Mei

AU - Lin, Chih Li

AU - Jhang, Ai Zhi

AU - Tsai, Jie Heng

AU - Badmaev, Vladimir

AU - Nagabhushanam, Kalyanam

AU - Ho, Chi-Tang

AU - Chen, Wei Jen

PY - 2011/5/1

Y1 - 2011/5/1

N2 - Scope: Se-methyl-L-selenocysteine (MSC), a naturally occurring organoselenium compound, has shown cancer chemopreventive activity against several types of cancer. Herein, the effect of MSC on the inflammatory response in lipopolysaccharide (LPS)-activated murine RAW 264.7 macrophage cells was investigated. Methods and results: The present results demonstrated that MSC markedly inhibited LPS-induced production of NO in a dose-dependent pattern with decreased mRNA and protein levels of inducible nitric oxide synthase (iNOS). MSC also reduced nuclear translocation of p65 and p50 subunits of nuclear factor-κB (NF-κB), a critical transcription factor necessary for iNOS expression, accompanied with downregulation of LPS-triggered NF-κB-dependent gene expression evaluating by a luciferase reporter. Inhibition of nuclear translocation by MSC might result from the prevention of the inhibitor of NF-κB from phosphorylation and consequent degradation via suppression inhibition of phosphorylation of IκB kinase α/β. Exploring the action mechanism involved, MSC can reduce the phosphorylation/activation of mitogen-activated protein kinases (MAPKs) related to NF-κB activation induced by LPS, including p38 MAPK and c-Jun N-terminal kinase in RAW 264.7 cells. Conclusion: MSC might contribute to the potent anti-inflammatory effect in LPS-activated RAW 264.7 cells via downregulation of NF-κB activation and iNOS expression, suggesting that MSC may be considered as a therapeutic candidate for chronic inflammatory diseases.

AB - Scope: Se-methyl-L-selenocysteine (MSC), a naturally occurring organoselenium compound, has shown cancer chemopreventive activity against several types of cancer. Herein, the effect of MSC on the inflammatory response in lipopolysaccharide (LPS)-activated murine RAW 264.7 macrophage cells was investigated. Methods and results: The present results demonstrated that MSC markedly inhibited LPS-induced production of NO in a dose-dependent pattern with decreased mRNA and protein levels of inducible nitric oxide synthase (iNOS). MSC also reduced nuclear translocation of p65 and p50 subunits of nuclear factor-κB (NF-κB), a critical transcription factor necessary for iNOS expression, accompanied with downregulation of LPS-triggered NF-κB-dependent gene expression evaluating by a luciferase reporter. Inhibition of nuclear translocation by MSC might result from the prevention of the inhibitor of NF-κB from phosphorylation and consequent degradation via suppression inhibition of phosphorylation of IκB kinase α/β. Exploring the action mechanism involved, MSC can reduce the phosphorylation/activation of mitogen-activated protein kinases (MAPKs) related to NF-κB activation induced by LPS, including p38 MAPK and c-Jun N-terminal kinase in RAW 264.7 cells. Conclusion: MSC might contribute to the potent anti-inflammatory effect in LPS-activated RAW 264.7 cells via downregulation of NF-κB activation and iNOS expression, suggesting that MSC may be considered as a therapeutic candidate for chronic inflammatory diseases.

KW - C-Jun N-terminal kinase (JNK)

KW - Inducible NO synthesis (iNOS)

KW - NF-κB

KW - P38 mitogen-activated protein kinase (p38 MAPK)

KW - Se-methyl-L-selenocysteine (MSC)

UR - http://www.scopus.com/inward/record.url?scp=79955571612&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79955571612&partnerID=8YFLogxK

U2 - https://doi.org/10.1002/mnfr.201000481

DO - https://doi.org/10.1002/mnfr.201000481

M3 - Article

C2 - 21213327

VL - 55

SP - 723

EP - 732

JO - Molecular Nutrition and Food Research

JF - Molecular Nutrition and Food Research

SN - 1613-4125

IS - 5

ER -