A Novel Synthetic Compound, YH-1118, Inhibited LPS-Induced Inflammatory Response by Suppressing IkappaB Kinase/NF-kappaB Pathway in Raw 264.7 Cells.
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.
['Yun|Chang Hyun|CH|', 'Jang|Eun Jung|EJ|', 'Kwon|Soon Cheon|SC|', 'Lee|Mee-Young|MY|', 'Lee|Sangku|S|', 'Oh|Sei-Ryang|SR|', 'Lee|Hyeong-Kyu|HK|', 'Ahn|Kyung-Seop|KS|', 'Lee|Ho-Jae|HJ|']
D000818:Animals D020869:Gene Expression Profiling D007166:Immunosuppressive Agents D007249:Inflammation D008070:Lipopolysaccharides D008264:Macrophages D051379:Mice D016328:NF-kappa B D009569:Nitric Oxide D052247:Nitric Oxide Synthase Type II D000067996:RAW 264.7 Cells
YH-1118 macrophages iNOS NF-κB inflammation