The Korean Journal of Physiology and Pharmacology

The Korean Society of Pharmacology (대한약리학회)
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Rifampicin Inhibits the LPS-induced Expression of Toll-like Receptor 2 via the Suppression of NF-${\kappa}B$ DNA-binding Activity in RAW 264.7 Cells

  • Kim, Seong-Keun (Institute of Hansen's Disease, College of Medicine, The Catholic University of Korea) ;
  • Kim, Young-Mi (Institute of Hansen's Disease, College of Medicine, The Catholic University of Korea) ;
  • Yeum, Chung-Eun (Institute of Hansen's Disease, College of Medicine, The Catholic University of Korea) ;
  • Jin, Song-Hyo (Institute of Hansen's Disease, College of Medicine, The Catholic University of Korea) ;
  • Chae, Gue-Tae (Institute of Hansen's Disease, College of Medicine, The Catholic University of Korea) ;
  • Lee, Seong-Beom (Institute of Hansen's Disease, College of Medicine, The Catholic University of Korea)
  • Published : 2009.12.31
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Abstract

Rifampicin is a macrocyclic antibiotic which is used extensively for treatment against Mycobacterium tuberculosis and other mycobacterial infections. Recently, a number of studies have focused on the immune-regulatory effects of rifampicin. Therefore, we hypothesized that rifampicin may influence the TLR2 expression in LPS-activated RAW 264.7 cells. In this study, we determined that rifampicin suppresses LPS-induced TLR2 mRNA expression. The down-regulation of TLR2 expression coincided with decreased production of TNF-$\alpha$ Since NF-${\kappa}B$ is a major transcription factor that regulates genes for TLR2 and TNF-$\alpha$, we examined the effect of rifampicin on the LPS-induced NF-${\kappa}B$ activation. Rifampicin inhibited NF-${\kappa}B$ DNA-binding activity in LPS-activated RAW 264.7 cells, while it did not affect IKK$\alpha/\beta$ activity. However, rifampicin slightly inhibited the nuclear translocation of NF-${\kappa}B$ p65. In addition, rifampicin increased physical interaction between pregnane X receptor, a receptor for rifampicin, and NF-${\kappa}B$ p65, suggesting pregnane X receptor interferes with NF-${\kappa}B$ binding to DNA. Taken together, our results demonstrate that rifampicin inhibits LPS-induced TLR2 expression, at least in part, via the suppression of NF-${\kappa}B$ DNA-binding activity in RAW 264.7 cells. Thus, the present results suggest that the rifampicin-mediated inhibition of TLR2 via the suppression of NF-${\kappa}B$ DNA-binding activity may be a novel mechanism of the immune-suppressive effects of rifampicin.

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