title: A Novel Synthetic Compound, YH-1118, Inhibited LPS-Induced Inflammatory Response by Suppressing IkappaB Kinase/NF-kappaB Pathway in Raw 264.7 Cells.
abstract: For the search of a potent first-in-class compound to inactivate macrophages responsible for inflammatory responses, in the present study, we investigated the anti-inflammatory effects of YH-1118, a novel synthetic compound, in a lipopolysaccharide (LPS)-stimulated mouse macrophage cell line, Raw 264.7. YH-1118 inhibited LPS-induced nitric oxide (NO) production and inducible NO synthase (iNOS) expression at both the protein and mRNA levels. The suppression of LPS-induced iNOS expression by YH-1118 was mediated via nuclear factor kappa B (NF-κB), but not activator protein-1 (AP-1) transcription factor. This was supported by the finding that YH-1118 attenuated the phosphorylation of inhibitor of κBα (IκBα) and nuclear translocation and DNA binding activity of NF-kappaB. Through the mechanisms that YH- 1118 inhibited the activation of IkappaB kinases (IKKs), upstream activators of NF-κB, or p38 MAPK, YH-1118 significantly suppressed LPS-induced production of pro-inflammatory cytokines, tumor necrosis factor-α, interleukin-1β (IL-1β), and IL-6 (p < 0.05). In conclusion, our results suggest that YH-1118 inhibits LPS-induced inflammatory responses by blocking IKK and NF-κB activation in macrophages, and may be a therapeutic candidate for the treatment of various inflammatory diseases.
authors.affiliation: Laboratory of Chemoprevention, Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon 406-840, Republic of Korea.
authors.forename: Chang Hyun
authors.initials: CH
authors.lastname: Yun
authors.affiliation: Laboratory of Chemoprevention, Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon 406-840, Republic of Korea.
authors.forename: Eun Jung
authors.initials: EJ
authors.lastname: Jang
authors.affiliation: Laboratory of Chemoprevention, Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon 406-840, Republic of Korea.
authors.forename: Soon Cheon
authors.initials: SC
authors.lastname: Kwon
authors.affiliation: Natural Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology, Chungbuk 363-883, Republic of Korea.
authors.forename: Mee-Young
authors.initials: MY
authors.lastname: Lee
authors.affiliation: Natural Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology, Chungbuk 363-883, Republic of Korea.
authors.forename: Sangku
authors.initials: S
authors.lastname: Lee
authors.affiliation: Natural Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology, Chungbuk 363-883, Republic of Korea.
authors.forename: Sei-Ryang
authors.initials: SR
authors.lastname: Oh
authors.affiliation: Natural Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology, Chungbuk 363-883, Republic of Korea.
authors.forename: Hyeong-Kyu
authors.initials: HK
authors.lastname: Lee
authors.affiliation: Natural Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology, Chungbuk 363-883, Republic of Korea.
authors.forename: Kyung-Seop
authors.initials: KS
authors.lastname: Ahn
authors.affiliation: Laboratory of Chemoprevention, Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon 406-840, Republic of Korea.
authors.forename: Ho-Jae
authors.initials: HJ
authors.lastname: Lee
mesh_terms: D000818:Animals; D020869:Gene Expression Profiling; D007166:Immunosuppressive Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D007249:Inflammation / Q000139:chemically induced*; D008070:Lipopolysaccharides / Q000633:toxicity*; D008264:Macrophages / Q000187:drug effects*; D051379:Mice; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D009569:Nitric Oxide / Q000032:analysis; D052247:Nitric Oxide Synthase Type II / Q000032:analysis; D000067996:RAW 264.7 Cells
chemical_list: D007166:Immunosuppressive Agents; D008070:Lipopolysaccharides; D016328:NF-kappa B; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse
keywords: NF-κB; YH-1118; iNOS; inflammation; macrophages