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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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The effect of quercetin on hyaluronan production induced by IL-1β or TNF-α in orbital fibroblasts.(A) Hyaluronan in media of confluent orbital fibroblast cultures from GO (n = 3) and normal (n = 3) individuals pretreated with 0, 10, 50 or 100 µM quercetin for 24 h before IL-1β stimulation (10 ng/ml, 16 h). (B) The effect of quercetin on hyaluronan production in GO orbital fibroblasts (n = 3) stimulated with IL-1β (10 ng/ml, 16 h) or TNF-α (10 ng/ml, 16 h). Triplicate measurements were averaged, and the data are expressed as mean values ± SD. *P<0.05 vs. cells stimulated with IL-1β or TNF-α alone.
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pone-0026261-g003: The effect of quercetin on hyaluronan production induced by IL-1β or TNF-α in orbital fibroblasts.(A) Hyaluronan in media of confluent orbital fibroblast cultures from GO (n = 3) and normal (n = 3) individuals pretreated with 0, 10, 50 or 100 µM quercetin for 24 h before IL-1β stimulation (10 ng/ml, 16 h). (B) The effect of quercetin on hyaluronan production in GO orbital fibroblasts (n = 3) stimulated with IL-1β (10 ng/ml, 16 h) or TNF-α (10 ng/ml, 16 h). Triplicate measurements were averaged, and the data are expressed as mean values ± SD. *P<0.05 vs. cells stimulated with IL-1β or TNF-α alone.

Mentions: Hyaluronan concentrations in culture medium did not differ significantly between unstimulated normal (367±85 ng/ml) and GO orbital fibroblasts (557±94 ng/ml; P = 0.07). However, the IL-1β-stimulated hyaluronan concentration was significantly higher in GO (1552±234 ng/ml) than in normal cultures (1191±198 ng/ml; P = 0.023). Quercetin pretreatment (50 and 100 µM) significantly reduced the IL-1β-induced hyaluronan release in both GO (1226 and 947 ng/ml, respectively) and normal cells (871 and 624 ng/ml, respectively; P<0.05; Fig. 3A). The effect of quercetin pretreatment on hyaluronan production induced by either IL-1β or TNF-α in GO orbital fibroblasts is shown in Fig. 3B. TNF-α (10 ng/ml) stimulated hyaluronan production to levels similar to those induced by IL-1β, and quercetin pretreatment significantly lowered this production in a dose-dependent manner (all P<0.05).


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)

The effect of quercetin on hyaluronan production induced by IL-1β or TNF-α in orbital fibroblasts.(A) Hyaluronan in media of confluent orbital fibroblast cultures from GO (n = 3) and normal (n = 3) individuals pretreated with 0, 10, 50 or 100 µM quercetin for 24 h before IL-1β stimulation (10 ng/ml, 16 h). (B) The effect of quercetin on hyaluronan production in GO orbital fibroblasts (n = 3) stimulated with IL-1β (10 ng/ml, 16 h) or TNF-α (10 ng/ml, 16 h). Triplicate measurements were averaged, and the data are expressed as mean values ± SD. *P<0.05 vs. cells stimulated with IL-1β or TNF-α alone.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3198474&req=5

pone-0026261-g003: The effect of quercetin on hyaluronan production induced by IL-1β or TNF-α in orbital fibroblasts.(A) Hyaluronan in media of confluent orbital fibroblast cultures from GO (n = 3) and normal (n = 3) individuals pretreated with 0, 10, 50 or 100 µM quercetin for 24 h before IL-1β stimulation (10 ng/ml, 16 h). (B) The effect of quercetin on hyaluronan production in GO orbital fibroblasts (n = 3) stimulated with IL-1β (10 ng/ml, 16 h) or TNF-α (10 ng/ml, 16 h). Triplicate measurements were averaged, and the data are expressed as mean values ± SD. *P<0.05 vs. cells stimulated with IL-1β or TNF-α alone.
Mentions: Hyaluronan concentrations in culture medium did not differ significantly between unstimulated normal (367±85 ng/ml) and GO orbital fibroblasts (557±94 ng/ml; P = 0.07). However, the IL-1β-stimulated hyaluronan concentration was significantly higher in GO (1552±234 ng/ml) than in normal cultures (1191±198 ng/ml; P = 0.023). Quercetin pretreatment (50 and 100 µM) significantly reduced the IL-1β-induced hyaluronan release in both GO (1226 and 947 ng/ml, respectively) and normal cells (871 and 624 ng/ml, respectively; P<0.05; Fig. 3A). The effect of quercetin pretreatment on hyaluronan production induced by either IL-1β or TNF-α in GO orbital fibroblasts is shown in Fig. 3B. TNF-α (10 ng/ml) stimulated hyaluronan production to levels similar to those induced by IL-1β, and quercetin pretreatment significantly lowered this production in a dose-dependent manner (all P<0.05).

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