PMID- 33122970 OWN - NLM STAT- MEDLINE DCOM- 20211006 LR - 20211006 IS - 1466-1861 (Electronic) IS - 0962-9351 (Print) IS - 0962-9351 (Linking) VI - 2020 DP - 2020 TI - Luteolin Attenuates IL-1beta-Induced THP-1 Adhesion to ARPE-19 Cells via Suppression of NF-kappaB and MAPK Pathways. PG - 9421340 LID - 10.1155/2020/9421340 [doi] LID - 9421340 AB - 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-1beta-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-) kappaB 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-1beta-stimulated increases of IL-6, IL-8, sICAM-1, and MCP-1 production by blocking the activation of MAPK and NF-kappaB signaling pathways, thus ameliorating the inflammatory response. CI - Copyright (c) 2020 Wen-Chung Huang et al. FAU - Huang, Wen-Chung AU - Huang WC AUID- ORCID: 0000-0001-7141-8971 AD - Graduate 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, Taiwan. AD - Division of Allergy, Asthma, and Rheumatology, Department of Pediatrics, Chang Gung Memorial Hospital, Linkou, Taoyuan City 33303, Taiwan. FAU - Liou, Chian-Jiun AU - Liou CJ AD - Division of Allergy, Asthma, and Rheumatology, Department of Pediatrics, Chang Gung Memorial Hospital, Linkou, Taoyuan City 33303, Taiwan. AD - Department of Nursing, Division of Basic Medical Sciences, Research Center for Chinese Herbal Medicine, and Graduate Institute of Health Industry Technology, Chang Gung University of Science and Technology, Taoyuan 33303, Taiwan. FAU - Shen, Szu-Chuan AU - Shen SC AD - Graduate Program of Nutrition Science, National Taiwan Normal University, 88 Ting-Chow Rd, Sec 4, Taipei, Taiwan. FAU - Hu, Sindy AU - Hu S AUID- ORCID: 0000-0002-4772-1169 AD - Department of Cosmetic Science, College of Human Ecology, Chang Gung University of Science and Technology, Guishan Dist., Taoyuan City 33303, Taiwan. AD - Department of Dermatology, Aesthetic Medical Center, Chang Gung Memorial Hospital, Linkou, Taoyuan City 33303, Taiwan. FAU - Hsiao, Chien-Yu AU - Hsiao CY AUID- ORCID: 0000-0003-3301-8808 AD - Department of Dermatology, Aesthetic Medical Center, Chang Gung Memorial Hospital, Linkou, Taoyuan City 33303, Taiwan. AD - Department of Nutrition and Health Sciences, Research Center for Chinese Herbal Medicine, College of Human Ecology, Chang Gung University of Science and Technology, Taoyuan City 33303, Taiwan. FAU - Wu, Shu-Ju AU - Wu SJ AUID- ORCID: 0000-0003-2370-9541 AD - Department of Dermatology, Aesthetic Medical Center, Chang Gung Memorial Hospital, Linkou, Taoyuan City 33303, Taiwan. AD - Department of Nutrition and Health Sciences, Research Center for Chinese Herbal Medicine, College of Human Ecology, Chang Gung University of Science and Technology, Taoyuan City 33303, Taiwan. LA - eng PT - Journal Article DEP - 20201016 PL - United States TA - Mediators Inflamm JT - Mediators of inflammation JID - 9209001 RN - 0 (Interleukin-1beta) RN - 0 (NF-kappa B) RN - EC 1.14.14.18 (Heme Oxygenase-1) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinases) RN - KUX1ZNC9J2 (Luteolin) SB - IM MH - Cell Line MH - Cell Survival/drug effects MH - Enzyme-Linked Immunosorbent Assay MH - Fluorescent Antibody Technique MH - Heme Oxygenase-1/metabolism MH - Humans MH - Interleukin-1beta/*pharmacology MH - Luteolin/*pharmacology MH - Mitogen-Activated Protein Kinases/*metabolism MH - NF-kappa B/*metabolism MH - Phosphorylation/drug effects MH - Proto-Oncogene Proteins c-akt/metabolism MH - THP-1 Cells PMC - PMC7585660 COIS- The authors declare that there is no conflict of interests regarding the publication of this paper. EDAT- 2020/10/31 06:00 MHDA- 2021/10/07 06:00 PMCR- 2020/10/16 CRDT- 2020/10/30 05:53 PHST- 2020/06/08 00:00 [received] PHST- 2020/07/23 00:00 [revised] PHST- 2020/08/04 00:00 [accepted] PHST- 2020/10/30 05:53 [entrez] PHST- 2020/10/31 06:00 [pubmed] PHST- 2021/10/07 06:00 [medline] PHST- 2020/10/16 00:00 [pmc-release] AID - 10.1155/2020/9421340 [doi] PST - epublish SO - Mediators Inflamm. 2020 Oct 16;2020:9421340. doi: 10.1155/2020/9421340. eCollection 2020.