Histone deacetylase inhibitor KBH-A42 inhibits cytokine production in RAW 264.7 macrophage cells and in vivo endotoxemia model
- Authors
- Choi, Yongseok; Park, Song-Kyu; Kim, Hwan Mook; Kang, Jong Soon; Yoon, Yeo Dae; Han, Sang Bae; Han, Jeung Whan; Yang, Jee Sun; Han, Gyoonhee
- Issue Date
- 31-10월-2008
- Publisher
- NATURE PUBLISHING GROUP
- Keywords
- anti-inflammatory agents; histone deacetylases; NF-kappa B; nitric oxide; transcription factor AP-1; tumor necrosis factor-alpha; vorinostat
- Citation
- EXPERIMENTAL AND MOLECULAR MEDICINE, v.40, no.5, pp.574 - 581
- Indexed
- SCIE
SCOPUS
KCI
- Journal Title
- EXPERIMENTAL AND MOLECULAR MEDICINE
- Volume
- 40
- Number
- 5
- Start Page
- 574
- End Page
- 581
- URI
- https://scholar.korea.ac.kr/handle/2021.sw.korea/122532
- DOI
- 10.3858/emm.2008.40.5.574
- ISSN
- 1226-3613
- Abstract
- In light of the anti-inflammatory properties of histone deacetylase (HDAC) inhibitors, such as suberoylanilide hydroxamic acid (SAHA) and trichostatin A (TSA), we examined a new HDAC inhibitor KBH-A42 for its anti-inflammatory activities. KBH-A42 showed noteworthy anti-inflammatory properties in vitro via suppression of the production of TNF-alpha, a proinflammatory cytokine, and nitric oxide (NO), a proinflammatory effector molecule, in LPS-stimulated RAW264.7 cells and peritoneal macrophages. It also inhibited TNF-alpha production in vivo as demonstrated in a LPS-induced mouse endotoxemia model. The levels of TNF-alpha, IL-1 beta, IL-6 and iNOS mRNAs determined by RT-PCR propose that the inhibition of these pro-inflammatory mediators by KBH-A42 resulted from inhibiting expression of these genes. However, the EMSA study to see the effect of KBH-A42 on the binding of NF-kappa B, a transcription factor, to a specific DNA sequence showed that the binding of NF-kappa B to DNA was not changed regardless of increasing the concentration of KBH-A42 in the presence and absence of LIPS stimulation. Interestingly, DNA binding of another transcription factor AP-1 dose-dependently increased by KBH-A42. KBH-A42 differentially regulated the phosphorylation of MAP kinases. While the phosphprylation of ERK1/2 and SAPK/JNK was not affected by KBH-A42, the phosphorylation of p38 decreased by KBH-A42. These results showed that KBH-A42 inhibits production of proinflammatory cytokines in macrophages by decreasing their mRNA levels, and p38 kinase is involved in the KBH-A42-mediated inhibition.
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Collections - Graduate School > Department of Biotechnology > 1. Journal Articles
- College of Pharmacy > Department of Pharmaceutical Science > 1. Journal Articles
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