title: YCG063 inhibits Pseudomonas aeruginosa LPS-induced inflammation in human retinal pigment epithelial cells through the TLR2-mediated AKT/NF-κB pathway and ROS-independent pathways.
abstract: YCG063 is known as an inhibitor of reactive oxygen species (ROS); however, its intracellular mechanisms of action remain poorly understood. In the present study, we investigated the effects of YCG063 on the inflammatory response of Pseudomonas aeruginosa lipopolysaccharide (PA-LPS)‑stimulated human retinal pigment epithelial cells (RPE cells). Human adult RPE cells (ARPE‑19) were stimulated with PA-LPS. We then investigated the LPS-induced expression of several inflammatory mediators, such as interleukin (IL)-6, IL-8, monocyte chemoattractant protein-1 (MCP-1) and intracellular adhesion molecule-1 (ICAM-1) in the ARPE-19 cells. We performed an enzyme-linked immunosorbent assay (ELISA), western blot analysis, electrophoretic mobility shift assay (EMSA) and fluorescence-activated cell sorting (FACS) to elucidate the mechanisms involved in the anti-inflammatory effects of YCG063 in the PA-LPS-stimulated cells. The results revealed that treatment with YCG063 significantly inhibited the levels of IL-6, IL-8, MCP-1 and ICAM-1 in the PA-LPS-stimulated ARPE-19 cells. YCG063 also markedly inhibited the phosphorylation of AKT in the PA‑LPS-stimulated cells. In addition, the activation of nuclear factor-κB (NF-κB) was also attenuated folllowing treatment with YCG063. ROS were not generated in the PA-LPS-stimulated cells. In conclusion, our data indicate that YCG063 may prove to be a potential protective agent against inflammation, possibly through the downregulation of Toll‑like receptor 2 (TLR2) and the AKT-dependent NF-κB activation pathway in PA-LPS-stimulated ARPE-19 cells. Furthermore, this anti-inflammatory activity occurred through ROS-independent signaling pathways.
authors.affiliation: Department of Neurosurgery, Busan Paik Hospital, Inje University College of Medicine, Busan, Republic of Korea.
authors.forename: Sung Hwa
authors.initials: SH
authors.lastname: Paeng
authors.affiliation: Department of Physiology, Kangwon National University School of Medicine, Chuncheon, Gangwon, Republic of Korea.
authors.forename: Won Sun
authors.initials: WS
authors.lastname: Park
authors.affiliation: Department of Biomedical Engineering, and Center for Marine-Integrated Biomedical Technology (BK21 Plus), Pukyong National University, Busan, Republic of Korea.
authors.forename: Won-Kyo
authors.initials: WK
authors.lastname: Jung
authors.affiliation: Marine Biodiversity Institute of Korea, Seocheon, Chungcheongnam-do, Republic of Korea.
authors.forename: Dae-Sung
authors.initials: DS
authors.lastname: Lee
authors.affiliation: Laboratory of Immunobiology, Department of Marine Life Sciences, Jeju National University, Jeju, Republic of Korea.
authors.forename: Gi-Young
authors.initials: GY
authors.lastname: Kim
authors.affiliation: Department of Biochemistry, College of Oriental Medicine, Dongeui University, Busan, Republic of Korea.
authors.forename: Yung Hyun
authors.initials: YH
authors.lastname: Choi
authors.affiliation: Department of Microbiology, Inje University College of Medicine, Busan, Republic of Korea.
authors.forename: Su-Kil
authors.initials: SK
authors.lastname: Seo
authors.affiliation: Department of Biochemistry, Inje University College of Medicine, Busan, Republic of Korea.
authors.forename: Won Hee
authors.initials: WH
authors.lastname: Jang
authors.affiliation: Department of Internal Medicine, Busan Paik Hospital, Inje University College of Medicine, Busan, Republic of Korea.
authors.forename: Jung Sik
authors.initials: JS
authors.lastname: Choi
authors.affiliation: Department of Internal Medicine, Busan Paik Hospital, Inje University College of Medicine, Busan, Republic of Korea.
authors.forename: Young-Min
authors.initials: YM
authors.lastname: Lee
authors.affiliation: Department of Microbiology, Inje University College of Medicine, Busan, Republic of Korea.
authors.forename: Saegwang
authors.initials: S
authors.lastname: Park
authors.affiliation: Department of Microbiology, Inje University College of Medicine, Busan, Republic of Korea.
authors.forename: Il-Whan
authors.initials: IW
authors.lastname: Choi
mesh_terms: D000328:Adult; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D006835:Hydrazones / Q000494:pharmacology*; D007249:Inflammation / Q000188:drug therapy* / Q000276:immunology / Q000382:microbiology*; D008070:Lipopolysaccharides / Q000276:immunology*; D016328:NF-kappa B / Q000276:immunology; D009593:Nitroimidazoles / Q000494:pharmacology*; D051057:Proto-Oncogene Proteins c-akt / Q000276:immunology; D011550:Pseudomonas aeruginosa / Q000276:immunology*; D017382:Reactive Oxygen Species / Q000276:immunology; D055213:Retinal Pigment Epithelium / Q000166:cytology / Q000187:drug effects* / Q000276:immunology / Q000382:microbiology; D015398:Signal Transduction / Q000187:drug effects; D051195:Toll-Like Receptor 2 / Q000276:immunology
chemical_list: D000893:Anti-Inflammatory Agents; D006835:Hydrazones; D008070:Lipopolysaccharides; D016328:NF-kappa B; D009593:Nitroimidazoles; D017382:Reactive Oxygen Species; D051195:Toll-Like Receptor 2; C555826:YCG 063; D051057:Proto-Oncogene Proteins c-akt