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

• Published in: Journal of microbiology and biotechnology Vol. 25; no. 7; pp. 1047 - 1055
• Main Authors: Yun, Chang Hyun, Jang, Eun Jung, Kwon, Soon Cheon, Lee, Mee-Young, Lee, Sangku, Oh, Sei-Ryang, Lee, Hyeong-Kyu, Ahn, Kyung-Seop, Lee, Ho-Jae
• Format: Journal Article
• Language: Korean
• Published: 2015
• Subjects: macrophages; inflammation; iNOS; YH-1118; NF- ${\kappa}B
• ISSN: 1017-7825; 1738-8872

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.