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The hydroxy-naphthoquinone lapachol arrests mycobacterial growth and immunomodulates host macrophages.

Abstract：

:The present study reports the anti-mycobacterial activity of 2-hydroxy-3-(3-methyl-2-butenyl)-1,4-naphthoquinone (lapachol) as well as its influence on macrophage functions. Lapachol (L) did not induce apoptosis/necrosis of THP-1 macrophages at ≤32 μg/mL. Mycobacterium avium liquid growth was arrested by ≥32 μg/mL and intra-macrophage proliferation by ≥16 μg/mL lapachol. The main immuno-modulatory effects of lapachol observed were an up-regulation of interferon-γ-receptor 1 (IFN-γR1) and major histocompatibility complex class II (MHCII) surface expression, and a marked inhibition of IL-10 secretion. Lapachol did not affect resting, IFN-γ- or toll-like receptor 2 (TLR2)-induced levels of oxygen and nitrogen metabolism key proteins nor the TLR2-mediated secretion of TNF-α, nor induced either oxidative or endoplasmic reticulum (ER) stress. Lapachol inhibited the surface expression of the co-stimulatory molecule CD86 but not that of CD80 and CD83. The results obtained indicate that the substituted naphthoquinone lapachol exhibits an anti-mycobacterial activity that is more efficient intra- than extra-cellularly, and exerts immuno-modulatory effects some of which may enhance the capacity of the host cell to control mycobacterial growth. The immune-modulatory action of lapachol could contribute to its more efficient intra-macrophage anti-mycobacterial activity.

journal_name

Int Immunopharmacol

journal_title

International immunopharmacology

authors

Oliveira RA,Azevedo-Ximenes E,Luzzati R,Garcia RC

doi

10.1016/j.intimp.2010.08.023

subject

Has Abstract

pub_date

2010-11-01 00:00:00

pages

1463-73

issue

11

eissn

1567-5769

issn

1878-1705

pii

S1567-5769(10)00277-8

journal_volume

10

pub_type

杂志文章

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