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

• 영문명: Rifampicin Inhibits the LPS-induced Expression of Toll-like Receptor 2 via the Suppression of NF-ՊB DNA-binding Activity in RAW 264.7 Cells
• 발행기관: 대한생리학회-대한약리학회
• 저자명: Seong Keun Kim Young Mi Kim Chung Eun Yeum Song-Hyo Jin Gue Tae Chae Seong-Beom Lee
• 간행물 정보: 『The Korean Journal of Physiology & Pharmacology』제13권 제6호, 475~482쪽, 전체 8쪽
• 주제분류: 의약학 > 의학일반
• 파일형태: PDF
• 발행일자: 2009.01.01

영문 초록

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

키워드

Rifampicin TLR2 LPS Pregnane X receptor NF-Պ B