Ocular inflammation and endoplasmic reticulum stress are attenuated by supplementation with grape polyphenols in human retinal pigmented epithelium cells and in C57BL/6 mice

Jung Heun Ha, Pollob Kumar Shil, Ping Zhu, Liwei Gu, Qiuhong Li, Soonkyu Chung

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Inflammation and endoplasmic reticulum (ER) stress are common denominators for vision-threatening diseases such as diabetic retinopathy and age-related macular degeneration. Based on our previous study, supplementation with muscadine grape polyphenols (MGPs) alleviated systemic insulin resistance and proinflammatory responses. In this study, we hypothesized that MGPs would also be effective in attenuating ocular inflammation and ER stress. We tested this hypothesis using the human retinal pigmented epithelium (ARPE-19) cells and C57BL/6 mice. In ARPE-19 cells, tumor necrosis factor-a-induced proinflammatory gene expression of interleukin (IL)-1ß, IL-6, and monocyte chemotactic protein-1 was decreased by 35.0%, 68.8%, and 62.5%, respectively, with MGP pretreatment, which was primarily due to the diminished mitogen-activated protein kinase activation and subsequent reduction of nuclear factor κ-B activation. Consistently, acute ocular inflammation and leukocyte infiltration were almost completely dampened (>95%) by MGP supplementation (100-200 mg/kg body weight) in C57BL/6 mice. Moreover, MGPs reduced inflammation-mediated loss of tight junctions and retinal permeability. To further investigate the protective roles of MGPs against ER stress, ARPE-19 cells were stimulated with thapsigargin. Pretreatment with MGPs significantly decreased the following: 1) ER stressmediated vascular endothelial growth factor secretion (3.47 ± 0.06 vs. 1.58 ± 0.02 μg/L, P < 0.0001), 2) unfolded protein response, and 3) early apoptotic cell death (64.4 ± 6.85 vs. 33.7 ± 4.32%, P = 0.0003). Collectively, we have demonstrated that MGP is effective in attenuating ocular inflammation and ER stress. Our work also suggests that MGP may provide a novel dietary strategy to prevent vision-threatening retinal diseases.

Original languageEnglish (US)
Pages (from-to)799-806
Number of pages8
JournalJournal of Nutrition
Volume144
Issue number6
DOIs
StatePublished - Jun 2014

Fingerprint

Endoplasmic Reticulum Stress
Vitis
Polyphenols
Inbred C57BL Mouse
Epithelium
Inflammation
Unfolded Protein Response
Retinal Diseases
Thapsigargin
Chemokine CCL2
Tight Junctions
Macular Degeneration
Diabetic Retinopathy
Mitogen-Activated Protein Kinases
Interleukin-1
Endoplasmic Reticulum
Vascular Endothelial Growth Factor A
Insulin Resistance
Permeability
Interleukin-6

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Nutrition and Dietetics

Cite this

Ocular inflammation and endoplasmic reticulum stress are attenuated by supplementation with grape polyphenols in human retinal pigmented epithelium cells and in C57BL/6 mice. / Ha, Jung Heun; Shil, Pollob Kumar; Zhu, Ping; Gu, Liwei; Li, Qiuhong; Chung, Soonkyu.

In: Journal of Nutrition, Vol. 144, No. 6, 06.2014, p. 799-806.

Research output: Contribution to journalArticle

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abstract = "Inflammation and endoplasmic reticulum (ER) stress are common denominators for vision-threatening diseases such as diabetic retinopathy and age-related macular degeneration. Based on our previous study, supplementation with muscadine grape polyphenols (MGPs) alleviated systemic insulin resistance and proinflammatory responses. In this study, we hypothesized that MGPs would also be effective in attenuating ocular inflammation and ER stress. We tested this hypothesis using the human retinal pigmented epithelium (ARPE-19) cells and C57BL/6 mice. In ARPE-19 cells, tumor necrosis factor-a-induced proinflammatory gene expression of interleukin (IL)-1{\ss}, IL-6, and monocyte chemotactic protein-1 was decreased by 35.0{\%}, 68.8{\%}, and 62.5{\%}, respectively, with MGP pretreatment, which was primarily due to the diminished mitogen-activated protein kinase activation and subsequent reduction of nuclear factor κ-B activation. Consistently, acute ocular inflammation and leukocyte infiltration were almost completely dampened (>95{\%}) by MGP supplementation (100-200 mg/kg body weight) in C57BL/6 mice. Moreover, MGPs reduced inflammation-mediated loss of tight junctions and retinal permeability. To further investigate the protective roles of MGPs against ER stress, ARPE-19 cells were stimulated with thapsigargin. Pretreatment with MGPs significantly decreased the following: 1) ER stressmediated vascular endothelial growth factor secretion (3.47 ± 0.06 vs. 1.58 ± 0.02 μg/L, P < 0.0001), 2) unfolded protein response, and 3) early apoptotic cell death (64.4 ± 6.85 vs. 33.7 ± 4.32{\%}, P = 0.0003). Collectively, we have demonstrated that MGP is effective in attenuating ocular inflammation and ER stress. Our work also suggests that MGP may provide a novel dietary strategy to prevent vision-threatening retinal diseases.",
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