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 ƒÊg/mL. Mycobacterium avium liquid growth was arrested by .32 ƒÊg/mL and intra-macrophage proliferation by .16 ƒÊg/mL lapachol. The main immuno-modulatory effects of lapachol observed were an up-regulation of interferon-ƒÁ-receptor 1 (IFN-ƒÁR1) and major histocompatibility complex class II (MHCII) surface expression, and a marked inhibition of IL-10 secretion. Lapachol did not affect resting, IFN-ƒÁ- or toll-like receptor 2 (TLR2)-induced levels of oxygen and nitrogen metabolism key proteins nor the TLR2-mediated secretion of TNF-ƒ¿, 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.

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

LUZZATI, ROBERTO;
2010-01-01

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 ƒÊg/mL. Mycobacterium avium liquid growth was arrested by .32 ƒÊg/mL and intra-macrophage proliferation by .16 ƒÊg/mL lapachol. The main immuno-modulatory effects of lapachol observed were an up-regulation of interferon-ƒÁ-receptor 1 (IFN-ƒÁR1) and major histocompatibility complex class II (MHCII) surface expression, and a marked inhibition of IL-10 secretion. Lapachol did not affect resting, IFN-ƒÁ- or toll-like receptor 2 (TLR2)-induced levels of oxygen and nitrogen metabolism key proteins nor the TLR2-mediated secretion of TNF-ƒ¿, 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.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11368/2303875
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