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
The Korean Journal of Physiology and Pharmacology
; : 475-482, 2009.
Article
de En
| WPRIM
| ID: wpr-727454
Bibliothèque responsable:
WPRO
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.
Mots clés
Texte intégral:
1
Indice:
WPRIM
Sujet Principal:
Rifampicine
/
Facteurs de transcription
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ADN
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ARN messager
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Récepteurs aux stéroïdes
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Régulation négative
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Facteur de transcription NF-kappa B
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Facteur de nécrose tumorale alpha
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Récepteurs de type Toll
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Récepteur de type Toll-2
langue:
En
Texte intégral:
The Korean Journal of Physiology and Pharmacology
Année:
2009
Type:
Article