Korean J Physiol Pharmacol.  2009 Dec;13(6):475-482. 10.4196/kjpp.2009.13.6.475.

Rifampicin Inhibits the LPS-induced Expression of Toll-like Receptor 2 via the Suppression of NF-kappaB DNA-binding Activity in RAW 264.7 Cells

Affiliations
  • 1Institute of Hansen's Disease, College of Medicine, The Catholic University of Korea, Seoul 137-701, Korea. sblee@catholic.ac.kr
  • 2Department of Pathology, College of Medicine, The Catholic University of Korea, Seoul 137-701, Korea.

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-kappaB is a major transcription factor that regulates genes for TLR2 and TNF-alpha, we examined the effect of rifampicin on the LPS-induced NF-kappaB activation. Rifampicin inhibited NF-kappaB DNA-binding activity in LPS-activated RAW 264.7 cells, while it did not affect IKKalpha/beta activity. However, rifampicin slightly inhibited the nuclear translocation of NF-kappaB p65. In addition, rifampicin increased physical interaction between pregnane X receptor, a receptor for rifampicin, and NF-kappaB p65, suggesting pregnane X receptor interferes with NF-kappaB binding to DNA. Taken together, our results demonstrate that rifampicin inhibits LPS-induced TLR2 expression, at least in part, via the suppression of NF-kappaB 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-kappaB DNA-binding activity may be a novel mechanism of the immune-suppressive effects of rifampicin.

Keyword

Rifampicin; TLR2; LPS; Pregnane X receptor; NF-kappaB

MeSH Terms

DNA
Down-Regulation
Mycobacterium tuberculosis
NF-kappa B
Receptors, Steroid
Rifampin
RNA, Messenger
Toll-Like Receptor 2
Toll-Like Receptors
Transcription Factors
Tumor Necrosis Factor-alpha
DNA
NF-kappa B
RNA, Messenger
Receptors, Steroid
Rifampin
Toll-Like Receptor 2
Toll-Like Receptors
Transcription Factors
Tumor Necrosis Factor-alpha
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