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Oleuropein Protects Human Retinal Pigment Epithelium Cells from IL-1β–Induced Inflammation by Blocking MAPK/NF-κB Signaling Pathways

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Abstract—

Proinflammatory mediators such as interleukin (IL)-1β cause retinal pigment epithelium (RPE) inflammation, which is related to visual deterioration, including age-related macular degeneration and diabetic retinopathy. Oleuropein is a polyphenol compound that shows potent anti-inflammatory, antioxidant, and anti-cancer activities, but its effects on IL-1β–induced inflammation have not been examined in the adult RPE cell line ARPE-19. Here, we assessed the ability of oleuropein to attenuate this inflammation in ARPE-19 cells. IL-1β induced secretion of the inflammatory cytokines IL-6, monocyte chemoattractant protein-1 (MCP)-1, and soluble intercellular adhesion molecule (sICAM)-1. As measured by enzyme-linked immunosorbent assay, oleuropein significantly inhibited levels of all three proteins and led to decreased monocyte adhesiveness to ARPE-19 cells. To clarify the underlying anti-inflammatory mechanisms, we used western blots to evaluate the effect of oleuropein on inactivation of the nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways. The results showed that oleuropein significantly decreased levels of the inflammatory mediator cyclooxygenase-2 and increased anti-inflammatory protein HO-1 expression. We next examined if the anti-inflammatory activity of oleuropein arises via inactivated NF-κB. We found that suppressing phosphorylation of the JNK1/2 and p38 MAPK signaling pathways inhibited IL-6, MCP-1, and sICAM-1 secretion, implicating these pathways and NF-κB suppression in the effects of oleuropein. These results indicate that oleuropein shows potential for the prevention and treatment of inflammatory diseases of the retina.

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AVAILABILITY OF DATA AND MATERIALS

The data that support the findings of this study are available from the corresponding author upon reasonable request.

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Funding

The present study was supported by grants from the Chang Gung Memorial Hospital (grants CMRPF1L0011, CMRPF1K0081, and CMRPF1H0111) and the Ministry of Science and Technology in Taiwan (grant 109–2320-B-255–006-MY3).

Author information

Author notes

  1. Ming-Lung Hsu and Wen-Chung Huang are equal contributors to the work.

Authors and Affiliations

  1. Department of Nutrition and Health Sciences, Research Center for Food and Cosmetic Safety, and Research Center for Chinese Herbal Medicine, College of Human Ecology, Guishan Dist, Chang Gung University of Science and Technology, No.261, Wenhua 1st Rd, Taoyuan City, 33303, Taiwan

    Ming-Lung Hsu, Yi-Rong Zhou & Shu-Ju Wu

  2. Graduate Institute of Health Industry Technology, Research Center for Industry of Human Ecology, Research Center for Chinese Herbal Medicine, College of Human Ecology, Guishan Dist, Chang Gung University of Science and Technology, No.261, Wenhua 1st Rd, Taoyuan City, 33303, Taiwan

    Wen-Chung Huang

  3. Division of Allergy, Asthma, and Rheumatology, Department of Pediatrics, Guishan Dist, Chang Gung Memorial Hospital, Linkou, 33303, Taiwan

    Wen-Chung Huang

  4. Aesthetic Medical Center, Department of Dermatology, Chang Gung Memorial Hospital, Guishan Dist, Taoyuan, 33303, Taiwan

    Sindy Hu, Chun‑Hsun Huang & Shu-Ju Wu

  5. Department of Cosmetic Science, Research Center for Food and Cosmetic Safety, and Research Center for Chinese Herbal Medicine, College of Human Ecology, Guishan Dist, Chang Gung University of Science and Technology, No.261, Wenhua 1st Rd, Taoyuan City, 33303, Taiwan

    Chun‑Hsun Huang

  6. Department of Nutrition and Health Sciences, Research Center for Food and Cosmetic Safety, and Research Center for Chinese Herbal Medicine, College of Human Ecology, Chang Gung University of Science and Technology, No.261, Wenhua 1st Rd., Guishan Dist., Taoyuan City, 33303, Taiwan

    Chun‑Hsun Huang & Shu-Ju Wu

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Contributions

Designed and performed the experiments: SJW, WCH, and CHH. Analysis and interpretation of data: MLH and YRZ. Drafting the manuscript: SJW and SH. All authors have read and agreed to the published version of the manuscript.

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Correspondence to Chun‑Hsun Huang or Shu-Ju Wu.

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Hsu, ML., Huang, WC., Zhou, YR. et al. Oleuropein Protects Human Retinal Pigment Epithelium Cells from IL-1β–Induced Inflammation by Blocking MAPK/NF-κB Signaling Pathways. Inflammation 45, 297–307 (2022). https://doi.org/10.1007/s10753-021-01546-4

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