Suppression of inducible cyclooxygenase and nitric oxide synthase through activation of peroxisome proliferator-activated receptor-γ by flavonoids in mouse macrophages

Yu-Chih Liang, Shu-Huei Tsai, De Cheng Tsai, Shoei Yn Lin-Shiau, J. K. Lin

Research output: Contribution to journalArticle

180 Citations (Scopus)

Abstract

Peroxisome proliferator-activated receptor (PPAR)γ transcription factor has been implicated in anti-inflammatory response. Of the compounds tested, apigenin, chrysin, and kaempferol significantly stimulated PPARγ transcriptional activity in a transient reporter assay. In addition, these three flavonoids strongly enhanced the inhibition of inducible cyclooxygenase and inducible nitric oxide synthase promoter activities in lipopolysaccharide-activated macrophages which contain the PPARγ expression plasmids. However, these three flavonoids exhibited weak PPARγ agonist activities in an in vitro competitive binding assay. Limited protease digestion of PPARγ suggested these three flavonoids produced a conformational change in PPARγ and the conformation differs in the receptor bound to BRL49653 versus these three flavonoids. These results suggested that these three flavonoids might act as allosteric effectors and were able to bind to PPARγ and activate it, but its binding site might be different from the natural ligand BRL49653.

Original languageEnglish
Pages (from-to)12-18
Number of pages7
JournalFEBS Letters
Volume496
Issue number1
DOIs
Publication statusPublished - May 4 2001

Fingerprint

Peroxisome Proliferator-Activated Receptors
Macrophages
Nitric Oxide Synthase Type II
Prostaglandin-Endoperoxide Synthases
Flavonoids
Nitric Oxide Synthase
Chemical activation
rosiglitazone
Assays
Apigenin
Competitive Binding
Lipopolysaccharides
Conformations
Digestion
Plasmids
Peptide Hydrolases
Anti-Inflammatory Agents
Transcription Factors
Binding Sites
Ligands

Keywords

  • Cyclooxygenase
  • Flavonoid
  • Inflammation
  • Lipopolysaccharide
  • Nitric oxide synthase
  • Peroxisome proliferator-activated receptor-γ

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

Suppression of inducible cyclooxygenase and nitric oxide synthase through activation of peroxisome proliferator-activated receptor-γ by flavonoids in mouse macrophages. / Liang, Yu-Chih; Tsai, Shu-Huei; Tsai, De Cheng; Lin-Shiau, Shoei Yn; Lin, J. K.

In: FEBS Letters, Vol. 496, No. 1, 04.05.2001, p. 12-18.

Research output: Contribution to journalArticle

@article{88ff65cb7b3b4eeaa3a78622f1e06629,
title = "Suppression of inducible cyclooxygenase and nitric oxide synthase through activation of peroxisome proliferator-activated receptor-γ by flavonoids in mouse macrophages",
abstract = "Peroxisome proliferator-activated receptor (PPAR)γ transcription factor has been implicated in anti-inflammatory response. Of the compounds tested, apigenin, chrysin, and kaempferol significantly stimulated PPARγ transcriptional activity in a transient reporter assay. In addition, these three flavonoids strongly enhanced the inhibition of inducible cyclooxygenase and inducible nitric oxide synthase promoter activities in lipopolysaccharide-activated macrophages which contain the PPARγ expression plasmids. However, these three flavonoids exhibited weak PPARγ agonist activities in an in vitro competitive binding assay. Limited protease digestion of PPARγ suggested these three flavonoids produced a conformational change in PPARγ and the conformation differs in the receptor bound to BRL49653 versus these three flavonoids. These results suggested that these three flavonoids might act as allosteric effectors and were able to bind to PPARγ and activate it, but its binding site might be different from the natural ligand BRL49653.",
keywords = "Cyclooxygenase, Flavonoid, Inflammation, Lipopolysaccharide, Nitric oxide synthase, Peroxisome proliferator-activated receptor-γ",
author = "Yu-Chih Liang and Shu-Huei Tsai and Tsai, {De Cheng} and Lin-Shiau, {Shoei Yn} and Lin, {J. K.}",
year = "2001",
month = "5",
day = "4",
doi = "10.1016/S0014-5793(01)02393-6",
language = "English",
volume = "496",
pages = "12--18",
journal = "FEBS Letters",
issn = "0014-5793",
publisher = "Elsevier",
number = "1",

}

TY - JOUR

T1 - Suppression of inducible cyclooxygenase and nitric oxide synthase through activation of peroxisome proliferator-activated receptor-γ by flavonoids in mouse macrophages

AU - Liang, Yu-Chih

AU - Tsai, Shu-Huei

AU - Tsai, De Cheng

AU - Lin-Shiau, Shoei Yn

AU - Lin, J. K.

PY - 2001/5/4

Y1 - 2001/5/4

N2 - Peroxisome proliferator-activated receptor (PPAR)γ transcription factor has been implicated in anti-inflammatory response. Of the compounds tested, apigenin, chrysin, and kaempferol significantly stimulated PPARγ transcriptional activity in a transient reporter assay. In addition, these three flavonoids strongly enhanced the inhibition of inducible cyclooxygenase and inducible nitric oxide synthase promoter activities in lipopolysaccharide-activated macrophages which contain the PPARγ expression plasmids. However, these three flavonoids exhibited weak PPARγ agonist activities in an in vitro competitive binding assay. Limited protease digestion of PPARγ suggested these three flavonoids produced a conformational change in PPARγ and the conformation differs in the receptor bound to BRL49653 versus these three flavonoids. These results suggested that these three flavonoids might act as allosteric effectors and were able to bind to PPARγ and activate it, but its binding site might be different from the natural ligand BRL49653.

AB - Peroxisome proliferator-activated receptor (PPAR)γ transcription factor has been implicated in anti-inflammatory response. Of the compounds tested, apigenin, chrysin, and kaempferol significantly stimulated PPARγ transcriptional activity in a transient reporter assay. In addition, these three flavonoids strongly enhanced the inhibition of inducible cyclooxygenase and inducible nitric oxide synthase promoter activities in lipopolysaccharide-activated macrophages which contain the PPARγ expression plasmids. However, these three flavonoids exhibited weak PPARγ agonist activities in an in vitro competitive binding assay. Limited protease digestion of PPARγ suggested these three flavonoids produced a conformational change in PPARγ and the conformation differs in the receptor bound to BRL49653 versus these three flavonoids. These results suggested that these three flavonoids might act as allosteric effectors and were able to bind to PPARγ and activate it, but its binding site might be different from the natural ligand BRL49653.

KW - Cyclooxygenase

KW - Flavonoid

KW - Inflammation

KW - Lipopolysaccharide

KW - Nitric oxide synthase

KW - Peroxisome proliferator-activated receptor-γ

UR - http://www.scopus.com/inward/record.url?scp=0035805144&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0035805144&partnerID=8YFLogxK

U2 - 10.1016/S0014-5793(01)02393-6

DO - 10.1016/S0014-5793(01)02393-6

M3 - Article

VL - 496

SP - 12

EP - 18

JO - FEBS Letters

JF - FEBS Letters

SN - 0014-5793

IS - 1

ER -