Luteolin Attenuates IL-1β-Induced THP-1 Adhesion to ARPE-19 Cells via Suppression of NF-κB and MAPK Pathways

Cytokine-induced endothelial dysfunction leads to inflammation and vascular adhesion molecule production in retinal pigment epithelium (RPE) cells. Inflammation is a critical mediator in retinal degeneration (RD) diseases, including age-related macular degeneration (AMD), and RD progression may be p...

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Main Authors: Wen-Chung Huang, Chian-Jiun Liou, Szu-Chuan Shen, Sindy Hu, Chien-Yu Hsiao, Shu-Ju Wu
Format: Article
Language:English
Published: Wiley 2020-01-01
Series:Mediators of Inflammation
Online Access:http://dx.doi.org/10.1155/2020/9421340
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author Wen-Chung Huang
Chian-Jiun Liou
Szu-Chuan Shen
Sindy Hu
Chien-Yu Hsiao
Shu-Ju Wu
author_facet Wen-Chung Huang
Chian-Jiun Liou
Szu-Chuan Shen
Sindy Hu
Chien-Yu Hsiao
Shu-Ju Wu
author_sort Wen-Chung Huang
collection DOAJ
description Cytokine-induced endothelial dysfunction leads to inflammation and vascular adhesion molecule production in retinal pigment epithelium (RPE) cells. Inflammation is a critical mediator in retinal degeneration (RD) diseases, including age-related macular degeneration (AMD), and RD progression may be prevented through anti-inflammatory activity in RPE cells. The flavonoid polyphenol luteolin (LU) has anti-inflammatory and antidiabetes activities, but its effects regarding retinal protection remain unknown. Here, we examined the ability of luteolin to alleviate markers of inflammation related to RD in cytokine-primed APPE-19 cells. We found that luteolin decreased the levels of interleukin- (IL-) 6, IL-8, soluble intercellular adhesion molecule-1 (sICAM-1), and monocyte chemoattractant protein-1 (MCP-1) and attenuated adherence of the human monocytic leukemia cell line THP-1 to IL-1β-stimulated ARPE-19 cells. Luteolin also increased anti-inflammatory protein heme oxygenase-1 (HO-1) levels. Interestingly, luteolin induced protein kinase B (AKT) phosphorylation, thus inhibiting nuclear factor- (NF-) κB transfer from cytoplasm into the nucleus and suppressing mitogen-activated protein kinase (MAPK) inflammatory pathways. Furthermore, cotreatment with MAPK inhibitors and luteolin decreased inflammatory cytokine and chemokine levels, and further suppressed THP-1 adhesion. Overall, these results provide evidence that luteolin protects ARPE-19 cells from IL-1β-stimulated increases of IL-6, IL-8, sICAM-1, and MCP-1 production by blocking the activation of MAPK and NF-κB signaling pathways, thus ameliorating the inflammatory response.
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spelling doaj-art-76c5e3c55ac64bf8809e44b619932c882025-02-03T01:28:18ZengWileyMediators of Inflammation0962-93511466-18612020-01-01202010.1155/2020/94213409421340Luteolin Attenuates IL-1β-Induced THP-1 Adhesion to ARPE-19 Cells via Suppression of NF-κB and MAPK PathwaysWen-Chung Huang0Chian-Jiun Liou1Szu-Chuan Shen2Sindy Hu3Chien-Yu Hsiao4Shu-Ju Wu5Graduate Institute of Health Industry Technology, Research Center for Food and Cosmetic Safety, College of Human Ecology, Chang Gung University of Science and Technology, Taoyuan City 33303, TaiwanDivision of Allergy, Asthma, and Rheumatology, Department of Pediatrics, Chang Gung Memorial Hospital, Linkou, Taoyuan City 33303, TaiwanGraduate Program of Nutrition Science, National Taiwan Normal University, 88 Ting-Chow Rd, Sec 4, Taipei, TaiwanDepartment of Cosmetic Science, College of Human Ecology, Chang Gung University of Science and Technology, Guishan Dist., Taoyuan City 33303, TaiwanDepartment of Dermatology, Aesthetic Medical Center, Chang Gung Memorial Hospital, Linkou, Taoyuan City 33303, TaiwanDepartment of Dermatology, Aesthetic Medical Center, Chang Gung Memorial Hospital, Linkou, Taoyuan City 33303, TaiwanCytokine-induced endothelial dysfunction leads to inflammation and vascular adhesion molecule production in retinal pigment epithelium (RPE) cells. Inflammation is a critical mediator in retinal degeneration (RD) diseases, including age-related macular degeneration (AMD), and RD progression may be prevented through anti-inflammatory activity in RPE cells. The flavonoid polyphenol luteolin (LU) has anti-inflammatory and antidiabetes activities, but its effects regarding retinal protection remain unknown. Here, we examined the ability of luteolin to alleviate markers of inflammation related to RD in cytokine-primed APPE-19 cells. We found that luteolin decreased the levels of interleukin- (IL-) 6, IL-8, soluble intercellular adhesion molecule-1 (sICAM-1), and monocyte chemoattractant protein-1 (MCP-1) and attenuated adherence of the human monocytic leukemia cell line THP-1 to IL-1β-stimulated ARPE-19 cells. Luteolin also increased anti-inflammatory protein heme oxygenase-1 (HO-1) levels. Interestingly, luteolin induced protein kinase B (AKT) phosphorylation, thus inhibiting nuclear factor- (NF-) κB transfer from cytoplasm into the nucleus and suppressing mitogen-activated protein kinase (MAPK) inflammatory pathways. Furthermore, cotreatment with MAPK inhibitors and luteolin decreased inflammatory cytokine and chemokine levels, and further suppressed THP-1 adhesion. Overall, these results provide evidence that luteolin protects ARPE-19 cells from IL-1β-stimulated increases of IL-6, IL-8, sICAM-1, and MCP-1 production by blocking the activation of MAPK and NF-κB signaling pathways, thus ameliorating the inflammatory response.http://dx.doi.org/10.1155/2020/9421340
spellingShingle Wen-Chung Huang
Chian-Jiun Liou
Szu-Chuan Shen
Sindy Hu
Chien-Yu Hsiao
Shu-Ju Wu
Luteolin Attenuates IL-1β-Induced THP-1 Adhesion to ARPE-19 Cells via Suppression of NF-κB and MAPK Pathways
Mediators of Inflammation
title Luteolin Attenuates IL-1β-Induced THP-1 Adhesion to ARPE-19 Cells via Suppression of NF-κB and MAPK Pathways
title_full Luteolin Attenuates IL-1β-Induced THP-1 Adhesion to ARPE-19 Cells via Suppression of NF-κB and MAPK Pathways
title_fullStr Luteolin Attenuates IL-1β-Induced THP-1 Adhesion to ARPE-19 Cells via Suppression of NF-κB and MAPK Pathways
title_full_unstemmed Luteolin Attenuates IL-1β-Induced THP-1 Adhesion to ARPE-19 Cells via Suppression of NF-κB and MAPK Pathways
title_short Luteolin Attenuates IL-1β-Induced THP-1 Adhesion to ARPE-19 Cells via Suppression of NF-κB and MAPK Pathways
title_sort luteolin attenuates il 1β induced thp 1 adhesion to arpe 19 cells via suppression of nf κb and mapk pathways
url http://dx.doi.org/10.1155/2020/9421340
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