A Novel Synthetic Compound, YH-1118, Inhibited LPS-Induced Inflammatory Response by Suppressing I kappa B Kinase/NF-kappa B Pathway in Raw 264.7 Cells
- Authors
- Yun, Chang Hyun; Jang, Eun Jung; Kwon, Soon Cheon; Lee, Mee-Young; Lee, Sartgku; Oh, Sei-Ryang; Lee, Hyeong-Kyu; Ahn, Kyung-Seop; Lee, Ho-Jae
- Issue Date
- Jul-2015
- Publisher
- KOREAN SOC MICROBIOLOGY & BIOTECHNOLOGY
- Keywords
- YH-1118; iNOS; NF-kappa B; macrophages; inflammation
- Citation
- JOURNAL OF MICROBIOLOGY AND BIOTECHNOLOGY, v.25, no.7, pp.1047 - 1055
- Journal Title
- JOURNAL OF MICROBIOLOGY AND BIOTECHNOLOGY
- Volume
- 25
- Number
- 7
- Start Page
- 1047
- End Page
- 1055
- URI
- https://scholarworks.bwise.kr/gachon/handle/2020.sw.gachon/10396
- DOI
- 10.4014/jmb.1504.04027
- ISSN
- 1017-7825
- 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-kappa B), but not activator protein-1 (AP-1) transcription factor. This was supported by the finding that YH-1118 attenuated the phosphorylation of inhibitor of kappa B alpha (I kappa B alpha) and nuclear translocation and DNA binding activity of NF-kappa B. Through the mechanisms that YH-1118 inhibited the activation of I kappa B kinases (IKKs), upstream activators of NF-kappa B, or p38 MAPK, YH-1118 significantly suppressed LPS-induced production of pro-inflammatory cytokines, tumor necrosis factor-alpha, interleukin-1 beta (IL-1 beta), and IL-6 (p < 0.05). In conclusion, our results suggest that YH-1118 inhibits LPS-induced inflammatory responses by blocking IKK and NF-kappa B activation in macrophages, and may be a therapeutic candidate for the treatment of various inflammatory diseases.
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