1-(2,3-Dibenzimidazol-2-ylpropyl)-2-methoxybenzene Is a Syk Inhibitor with Anti-Inflammatory Propertiesopen access
- Authors
- Kim, E[Kim, Eunji]; Son, YJ[Son, Young-Jin]; Yang, Y[Yang, Yanyan]; Shen, T[Shen, Ting]; Kim, I[Kim, Ikyon]; Aravinthan, A[Aravinthan, Adithan]; Kim, JH[Kim, Jong-Hoon]; Cho, JY[Cho, Jae Youl]
- Issue Date
- Apr-2016
- Publisher
- MDPI AG
- Citation
- MOLECULES, v.21, no.4
- Indexed
- SCIE
SCOPUS
- Journal Title
- MOLECULES
- Volume
- 21
- Number
- 4
- URI
- https://scholarworks.bwise.kr/skku/handle/2021.sw.skku/37164
- DOI
- 10.3390/molecules21040508
- ISSN
- 1420-3049
- Abstract
- Inflammation is the protective action of our bodies against external pathogens by recognition of pathogen-associated molecular patterns (PAMPs) via pattern recognition receptors (PRRs). Proper regulation of inflammatory responses is required to maintain our body's homeostasis, as well as there are demands to develop proper acute or chronic inflammation. In this study, we elucidated the regulatory mechanism of NF-kappa B-mediated inflammatory responses by a novel compound, 1-(2,3-dibenzimidazol-2-ylpropyl)-2-methoxybenzene (DBMB). We found that DBMB suppressed inflammatory mediators, nitric oxide (NO) and prostaglandin E-2 (PGE(2)), reacted to exposure to a number of toll like receptor (TLR) ligands. Such observations occurred following to decreased mRNA expression of several pro-inflammatory mediators, and such diminished mRNA levels were caused by inhibited transcriptional factor nuclear factor (NF)-kappa B, as evaluated by luciferase reporter assay and molecular biological approaches. To find the potential targets of DBMB, we screened phosphorylated forms of NF-kappa B signal molecules: inhibitor of kappa B alpha (I kappa B alpha), I kappa B kinase (IKK)alpha/beta, Akt, 3-phosphoinositide dependent protein kinase-1 (PDK1), p85, and spleen tyrosine kinase (Syk). We found that DBMB treatment could suppress signal transduction through these molecules. Additionally, we conducted in vitro kinase assays using immunoprecipitated Syk and its substrate, p85. Consequently, we could say that DBMB clearly suppressed the kinase activity of Syk kinase activity. Together, our results demonstrate that synthetic DBMB has an effect on the inflammatory NF-kappa B signaling pathway and suggest the potential for clinical use in the treatment of inflammatory diseases.
- Files in This Item
- There are no files associated with this item.
- Appears in
Collections - Biotechnology and Bioengineering > Integrative Biotechnology > 1. Journal Articles
- Biotechnology and Bioengineering > Department of Genetic Engineering > 1. Journal Articles
Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.