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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 adipogenesis in GO orbital fibroblasts.(A–B) Quercetin (50 or 100 µM) treatment for the first 3 days after initiation of 10-day adipogenesis in adipogenic media containing (A) 10 µM rosiglitazone, or (B) combined 10 µM rosiglitazone and 10 ng/ml IL-1β. Cells were stained with Oil Red O and examined grossly and microscopically (×40; inset ×400). (C) Cell-bound Oil Red O was solubilized and optical density (OD) read at 490 nm to obtain a quantitative assessment of adipogenesis. The experiments were performed in triplicate with cells from three different donors, and data in the column are the mean relative density ratios ± SD of three experiments. *P<0.001 vs. untreated control differentiated cells.
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pone-0026261-g005: Effect of quercetin on adipogenesis in GO orbital fibroblasts.(A–B) Quercetin (50 or 100 µM) treatment for the first 3 days after initiation of 10-day adipogenesis in adipogenic media containing (A) 10 µM rosiglitazone, or (B) combined 10 µM rosiglitazone and 10 ng/ml IL-1β. Cells were stained with Oil Red O and examined grossly and microscopically (×40; inset ×400). (C) Cell-bound Oil Red O was solubilized and optical density (OD) read at 490 nm to obtain a quantitative assessment of adipogenesis. The experiments were performed in triplicate with cells from three different donors, and data in the column are the mean relative density ratios ± SD of three experiments. *P<0.001 vs. untreated control differentiated cells.

Mentions: Oil Red O staining showed that quercetin dose-dependently decreased the size and number of intracytoplasmic lipid droplets in cells treated with either rosiglitazone alone or in combination with IL-1β (Fig. 5A and B). The optical density of stained cell lysates was measured to evaluate adipocyte differentiation quantitatively (Fig. 5C). Quercetin-treated cells showed significantly decreased absorbance at 490 nm in a dose-dependent manner (P<0.001). IL-1β treatment stimulated higher lipid accumulation levels, and the stimulatory effect was inhibited by quercetin (P<0.001).


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 adipogenesis in GO orbital fibroblasts.(A–B) Quercetin (50 or 100 µM) treatment for the first 3 days after initiation of 10-day adipogenesis in adipogenic media containing (A) 10 µM rosiglitazone, or (B) combined 10 µM rosiglitazone and 10 ng/ml IL-1β. Cells were stained with Oil Red O and examined grossly and microscopically (×40; inset ×400). (C) Cell-bound Oil Red O was solubilized and optical density (OD) read at 490 nm to obtain a quantitative assessment of adipogenesis. The experiments were performed in triplicate with cells from three different donors, and data in the column are the mean relative density ratios ± SD of three experiments. *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-g005: Effect of quercetin on adipogenesis in GO orbital fibroblasts.(A–B) Quercetin (50 or 100 µM) treatment for the first 3 days after initiation of 10-day adipogenesis in adipogenic media containing (A) 10 µM rosiglitazone, or (B) combined 10 µM rosiglitazone and 10 ng/ml IL-1β. Cells were stained with Oil Red O and examined grossly and microscopically (×40; inset ×400). (C) Cell-bound Oil Red O was solubilized and optical density (OD) read at 490 nm to obtain a quantitative assessment of adipogenesis. The experiments were performed in triplicate with cells from three different donors, and data in the column are the mean relative density ratios ± SD of three experiments. *P<0.001 vs. untreated control differentiated cells.
Mentions: Oil Red O staining showed that quercetin dose-dependently decreased the size and number of intracytoplasmic lipid droplets in cells treated with either rosiglitazone alone or in combination with IL-1β (Fig. 5A and B). The optical density of stained cell lysates was measured to evaluate adipocyte differentiation quantitatively (Fig. 5C). Quercetin-treated cells showed significantly decreased absorbance at 490 nm in a dose-dependent manner (P<0.001). IL-1β treatment stimulated higher lipid accumulation levels, and the stimulatory effect was inhibited by quercetin (P<0.001).

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