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http://dx.doi.org/10.4014/jmb.1504.04027

A Novel Synthetic Compound, YH-1118, Inhibited LPS-Induced Inflammatory Response by Suppressing IκB Kinase/NF-κB Pathway in Raw 264.7 Cells  

Yun, Chang Hyun (Laboratory of Chemoprevention, Lee Gil Ya Cancer and Diabetes Institute, Gachon University)
Jang, Eun Jung (Laboratory of Chemoprevention, Lee Gil Ya Cancer and Diabetes Institute, Gachon University)
Kwon, Soon Cheon (Laboratory of Chemoprevention, Lee Gil Ya Cancer and Diabetes Institute, Gachon University)
Lee, Mee-Young (Natural Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology)
Lee, Sangku (Natural Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology)
Oh, Sei-Ryang (Natural Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology)
Lee, Hyeong-Kyu (Natural Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology)
Ahn, Kyung-Seop (Natural Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology)
Lee, Ho-Jae (Laboratory of Chemoprevention, Lee Gil Ya Cancer and Diabetes Institute, Gachon University)
Publication Information
Journal of Microbiology and Biotechnology / v.25, no.7, 2015 , pp. 1047-1055 More about this Journal
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-nflammatory 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-κB. Through the mechanisms that YH-1118 inhibited the activation of IκB 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.
Keywords
YH-1118; iNOS; NF-${\kappa}B$; macrophages; inflammation;
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