期刊
INFLAMMATION
卷 45, 期 1, 页码 297-307出版社
SPRINGER/PLENUM PUBLISHERS
DOI: 10.1007/s10753-021-01546-4
关键词
oleuropein; ARPE-19; IL-1 beta; MAPK; NF-kappa B
资金
- Chang Gung Memorial Hospital [CMRPF1L0011, CMRPF1K0081, CMRPF1H0111]
- Ministry of Science and Technology in Taiwan [109-2320-B-255-006-MY3]
Oleuropein demonstrates potential in attenuating IL-1 beta-induced inflammation in adult RPE cells by inhibiting NF-kappa B and MAPK signaling pathways, reducing secretion of inflammatory cytokines, and showing anti-inflammatory effects. The results suggest that oleuropein may be useful in the prevention and treatment of inflammatory diseases in the retina.
Proinflammatory mediators such as interleukin (IL)-1 beta 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-1 beta-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-1 beta 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-kappa B) 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-kappa B. 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-kappa B 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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