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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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Effect of quercetin on the expression of adipogenic transcriptional regulators in differentiated orbital fibroblasts from GO patients.(A) Quercetin (50 or 100 µM) treatment for the first 3 days after initiation of 10-day adipogenesis in adipogenic media containing 10 µM rosiglitazone, or combined 10 µM rosiglitazone and 10 ng/ml IL-1β. After 10 days, cell lysates were subjected to western blot analysis of PPARγ, C/EBPα, and C/EBPβ protein expression. The experiments were performed in triplicate with cells from three different donors. (B–D) Quantification by densitometry, normalized to the β-actin level in the same sample, is shown for PPARγ (B), C/EBPα (C), and C/EBPβ (D). The data in the column are the mean relative density ratios ± SD of three experiments. *P<0.05, **P<0.001 vs. untreated control differentiated cells.
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pone-0026261-g006: Effect of quercetin on the expression of adipogenic transcriptional regulators in differentiated orbital fibroblasts from GO patients.(A) Quercetin (50 or 100 µM) treatment for the first 3 days after initiation of 10-day adipogenesis in adipogenic media containing 10 µM rosiglitazone, or combined 10 µM rosiglitazone and 10 ng/ml IL-1β. After 10 days, cell lysates were subjected to western blot analysis of PPARγ, C/EBPα, and C/EBPβ protein expression. The experiments were performed in triplicate with cells from three different donors. (B–D) Quantification by densitometry, normalized to the β-actin level in the same sample, is shown for PPARγ (B), C/EBPα (C), and C/EBPβ (D). The data in the column are the mean relative density ratios ± SD of three experiments. *P<0.05, **P<0.001 vs. untreated control differentiated cells.

Mentions: Western blot analysis was performed to investigate whether quercetin affects the expression of adipogenic transcription factors. As shown in Fig. 6, peroxisome proliferator-activated receptor (PPAR) γ and CCAAT/enhancer-binding proteins (C/EBP) α and β were all strongly enhanced in cells treated with either rosiglitazone or IL-1β. The protein levels were all further increased by the combination of rosiglitazone and IL-1β. Quercetin dose-dependently and significantly attenuated the expression of PPARγ, C/EBPα, and C/EBPβ in differentiated fibroblasts treated with rosiglitazone, with or without IL-1β (Fig. 6A, B, C, and D).


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)

Effect of quercetin on the expression of adipogenic transcriptional regulators in differentiated orbital fibroblasts from GO patients.(A) Quercetin (50 or 100 µM) treatment for the first 3 days after initiation of 10-day adipogenesis in adipogenic media containing 10 µM rosiglitazone, or combined 10 µM rosiglitazone and 10 ng/ml IL-1β. After 10 days, cell lysates were subjected to western blot analysis of PPARγ, C/EBPα, and C/EBPβ protein expression. The experiments were performed in triplicate with cells from three different donors. (B–D) Quantification by densitometry, normalized to the β-actin level in the same sample, is shown for PPARγ (B), C/EBPα (C), and C/EBPβ (D). The data in the column are the mean relative density ratios ± SD of three experiments. *P<0.05, **P<0.001 vs. untreated control differentiated cells.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3198474&req=5

pone-0026261-g006: Effect of quercetin on the expression of adipogenic transcriptional regulators in differentiated orbital fibroblasts from GO patients.(A) Quercetin (50 or 100 µM) treatment for the first 3 days after initiation of 10-day adipogenesis in adipogenic media containing 10 µM rosiglitazone, or combined 10 µM rosiglitazone and 10 ng/ml IL-1β. After 10 days, cell lysates were subjected to western blot analysis of PPARγ, C/EBPα, and C/EBPβ protein expression. The experiments were performed in triplicate with cells from three different donors. (B–D) Quantification by densitometry, normalized to the β-actin level in the same sample, is shown for PPARγ (B), C/EBPα (C), and C/EBPβ (D). The data in the column are the mean relative density ratios ± SD of three experiments. *P<0.05, **P<0.001 vs. untreated control differentiated cells.
Mentions: Western blot analysis was performed to investigate whether quercetin affects the expression of adipogenic transcription factors. As shown in Fig. 6, peroxisome proliferator-activated receptor (PPAR) γ and CCAAT/enhancer-binding proteins (C/EBP) α and β were all strongly enhanced in cells treated with either rosiglitazone or IL-1β. The protein levels were all further increased by the combination of rosiglitazone and IL-1β. Quercetin dose-dependently and significantly attenuated the expression of PPARγ, C/EBPα, and C/EBPβ in differentiated fibroblasts treated with rosiglitazone, with or without IL-1β (Fig. 6A, B, C, and D).

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