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Quercetin inhibits IL-1β-induced inflammation, hyaluronan production and adipogenesis in orbital fibroblasts from Graves' orbitopathy.

Yoon JS, Lee HJ, Choi SH, Chang EJ, Lee SY, Lee EJ - PLoS ONE (2011)

Bottom Line: Management of Graves' orbitopathy (GO) is challenging, as no reliable, specific, and safe medical therapeutic agents have yet been developed.Treatment with noncytotoxic doses of quercetin inhibited accumulation of intracytoplasmic lipid droplets and resulted in a dose-dependent decrease in expression of peroxisome proliferator-activated receptor γ, CCAAT/enhancer-binding protein (C/EBP) α, and C/EBPβ proteins.In conclusion, inhibition of inflammation, hyaluronan production, and adipogenesis by the natural plant product quercetin in vitro provides the basis for further study of its potential use in the treatment of GO.

View Article: PubMed Central - PubMed

Affiliation: Institute of Vision Research, Department of Ophthalmology, Yonsei University College of Medicine, Seoul, Korea.

ABSTRACT
Management of Graves' orbitopathy (GO) is challenging, as no reliable, specific, and safe medical therapeutic agents have yet been developed. We investigated the effect of quercetin in primary cultured orbital fibroblasts from GO, targeting pathways of inflammation, aberrant accumulation of extracellular matrix macromolecules, and adipose tissue expansion. Quercetin significantly attenuated intercellular adhesion molecule-1 (ICAM-1), interleukin (IL) -6, IL-8, and cyclooxygenase (COX) -2 mRNA expression, and inhibited IL-1β-induced increases in ICAM-1, IL-6, and IL-8 mRNA. Increased hyaluronan production induced by IL-1β or tumor necrosis factor-α was suppressed by quercetin in a dose- and time-dependent manner. Treatment with noncytotoxic doses of quercetin inhibited accumulation of intracytoplasmic lipid droplets and resulted in a dose-dependent decrease in expression of peroxisome proliferator-activated receptor γ, CCAAT/enhancer-binding protein (C/EBP) α, and C/EBPβ proteins. In conclusion, inhibition of inflammation, hyaluronan production, and adipogenesis by the natural plant product quercetin in vitro provides the basis for further study of its potential use in the treatment of GO.

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Effects of quercetin on ICAM-1, IL-6, IL-8, and COX-2 mRNA expression in Graves' orbitopathy (GO) orbital fibroblasts.(A) Orbital fibroblasts (5×105) from GO patients pretreated with 0, 50, or 100 µM quercetin for 24 h were used to analyze for ICAM-1, IL-6, IL-8, and COX-2 mRNA expression by RT-PCR. (B) Cells pretreated as in (A) were then stimulated with IL-1β (10 ng/ml) for 16 h, and were then used for RT-PCR analyses. (C) RT-PCR analysis of ICAM-1, IL-6, IL-8, and COX-2 mRNA expression, with values determined by densitometry and normalized to GAPDH. Cells had been pretreated with 100 µM quercetin for 6, 9, or 24 h, then stimulated with IL-1β (10 ng/ml) for 16 h. Data in each column above represent the mean relative density ratio ± SD of three experiments, and representative gel images are shown below the graphs. Differences between treated and untreated cells (*P<0.05, **P<0.001) are indicated.
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pone-0026261-g002: Effects of quercetin on ICAM-1, IL-6, IL-8, and COX-2 mRNA expression in Graves' orbitopathy (GO) orbital fibroblasts.(A) Orbital fibroblasts (5×105) from GO patients pretreated with 0, 50, or 100 µM quercetin for 24 h were used to analyze for ICAM-1, IL-6, IL-8, and COX-2 mRNA expression by RT-PCR. (B) Cells pretreated as in (A) were then stimulated with IL-1β (10 ng/ml) for 16 h, and were then used for RT-PCR analyses. (C) RT-PCR analysis of ICAM-1, IL-6, IL-8, and COX-2 mRNA expression, with values determined by densitometry and normalized to GAPDH. Cells had been pretreated with 100 µM quercetin for 6, 9, or 24 h, then stimulated with IL-1β (10 ng/ml) for 16 h. Data in each column above represent the mean relative density ratio ± SD of three experiments, and representative gel images are shown below the graphs. Differences between treated and untreated cells (*P<0.05, **P<0.001) are indicated.

Mentions: We first examined intercellular adhesion molecule (ICAM) -1, IL-6, IL-8 and cyclooxygenase (COX)-2 gene expression in the absence or presence of quercetin (50 or 100 µM for 24 h), evaluated in both GO and normal orbital fibroblasts by reverse transcription-polymerase chain reaction (RT-PCR). These proinflammatory molecules were virtually undetectable in untreated normal cell cultures (data not shown) but were detectable in GO cells, and expression was decreased significantly by quercetin pretreatment in a dose-dependent manner (Fig. 2A).


Quercetin inhibits IL-1β-induced inflammation, hyaluronan production and adipogenesis in orbital fibroblasts from Graves' orbitopathy.

Yoon JS, Lee HJ, Choi SH, Chang EJ, Lee SY, Lee EJ - PLoS ONE (2011)

Effects of quercetin on ICAM-1, IL-6, IL-8, and COX-2 mRNA expression in Graves' orbitopathy (GO) orbital fibroblasts.(A) Orbital fibroblasts (5×105) from GO patients pretreated with 0, 50, or 100 µM quercetin for 24 h were used to analyze for ICAM-1, IL-6, IL-8, and COX-2 mRNA expression by RT-PCR. (B) Cells pretreated as in (A) were then stimulated with IL-1β (10 ng/ml) for 16 h, and were then used for RT-PCR analyses. (C) RT-PCR analysis of ICAM-1, IL-6, IL-8, and COX-2 mRNA expression, with values determined by densitometry and normalized to GAPDH. Cells had been pretreated with 100 µM quercetin for 6, 9, or 24 h, then stimulated with IL-1β (10 ng/ml) for 16 h. Data in each column above represent the mean relative density ratio ± SD of three experiments, and representative gel images are shown below the graphs. Differences between treated and untreated cells (*P<0.05, **P<0.001) are indicated.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3198474&req=5

pone-0026261-g002: Effects of quercetin on ICAM-1, IL-6, IL-8, and COX-2 mRNA expression in Graves' orbitopathy (GO) orbital fibroblasts.(A) Orbital fibroblasts (5×105) from GO patients pretreated with 0, 50, or 100 µM quercetin for 24 h were used to analyze for ICAM-1, IL-6, IL-8, and COX-2 mRNA expression by RT-PCR. (B) Cells pretreated as in (A) were then stimulated with IL-1β (10 ng/ml) for 16 h, and were then used for RT-PCR analyses. (C) RT-PCR analysis of ICAM-1, IL-6, IL-8, and COX-2 mRNA expression, with values determined by densitometry and normalized to GAPDH. Cells had been pretreated with 100 µM quercetin for 6, 9, or 24 h, then stimulated with IL-1β (10 ng/ml) for 16 h. Data in each column above represent the mean relative density ratio ± SD of three experiments, and representative gel images are shown below the graphs. Differences between treated and untreated cells (*P<0.05, **P<0.001) are indicated.
Mentions: We first examined intercellular adhesion molecule (ICAM) -1, IL-6, IL-8 and cyclooxygenase (COX)-2 gene expression in the absence or presence of quercetin (50 or 100 µM for 24 h), evaluated in both GO and normal orbital fibroblasts by reverse transcription-polymerase chain reaction (RT-PCR). These proinflammatory molecules were virtually undetectable in untreated normal cell cultures (data not shown) but were detectable in GO cells, and expression was decreased significantly by quercetin pretreatment in a dose-dependent manner (Fig. 2A).

Bottom Line: Management of Graves' orbitopathy (GO) is challenging, as no reliable, specific, and safe medical therapeutic agents have yet been developed.Treatment with noncytotoxic doses of quercetin inhibited accumulation of intracytoplasmic lipid droplets and resulted in a dose-dependent decrease in expression of peroxisome proliferator-activated receptor γ, CCAAT/enhancer-binding protein (C/EBP) α, and C/EBPβ proteins.In conclusion, inhibition of inflammation, hyaluronan production, and adipogenesis by the natural plant product quercetin in vitro provides the basis for further study of its potential use in the treatment of GO.

View Article: PubMed Central - PubMed

Affiliation: Institute of Vision Research, Department of Ophthalmology, Yonsei University College of Medicine, Seoul, Korea.

ABSTRACT
Management of Graves' orbitopathy (GO) is challenging, as no reliable, specific, and safe medical therapeutic agents have yet been developed. We investigated the effect of quercetin in primary cultured orbital fibroblasts from GO, targeting pathways of inflammation, aberrant accumulation of extracellular matrix macromolecules, and adipose tissue expansion. Quercetin significantly attenuated intercellular adhesion molecule-1 (ICAM-1), interleukin (IL) -6, IL-8, and cyclooxygenase (COX) -2 mRNA expression, and inhibited IL-1β-induced increases in ICAM-1, IL-6, and IL-8 mRNA. Increased hyaluronan production induced by IL-1β or tumor necrosis factor-α was suppressed by quercetin in a dose- and time-dependent manner. Treatment with noncytotoxic doses of quercetin inhibited accumulation of intracytoplasmic lipid droplets and resulted in a dose-dependent decrease in expression of peroxisome proliferator-activated receptor γ, CCAAT/enhancer-binding protein (C/EBP) α, and C/EBPβ proteins. In conclusion, inhibition of inflammation, hyaluronan production, and adipogenesis by the natural plant product quercetin in vitro provides the basis for further study of its potential use in the treatment of GO.

Show MeSH
Related in: MedlinePlus