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.
Copyright © 2010 Elsevier B.V. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Anti-Bacterial Agents / pharmacology*
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Antigens, CD / analysis
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Antigens, CD / immunology
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B7-1 Antigen / analysis
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B7-1 Antigen / immunology
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B7-2 Antigen / analysis
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B7-2 Antigen / immunology
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CD83 Antigen
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Cell Line
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Histocompatibility Antigens Class II / immunology
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Humans
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Immunoglobulins / analysis
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Immunoglobulins / immunology
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Immunologic Factors / pharmacology*
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Immunomodulation / drug effects*
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Interferon gamma Receptor
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Interferon-gamma / analysis
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Interferon-gamma / immunology
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Interleukin-10 / immunology
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Interleukin-10 / metabolism
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Macrophages / drug effects*
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Macrophages / immunology
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Membrane Glycoproteins / analysis
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Membrane Glycoproteins / immunology
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Mycobacterium avium / drug effects*
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Naphthoquinones / pharmacology*
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Nitrogen / metabolism
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Oxidative Stress / drug effects
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Oxidative Stress / immunology
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Oxygen / metabolism
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Receptors, Interferon / analysis
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Receptors, Interferon / immunology
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Toll-Like Receptor 2 / analysis
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Toll-Like Receptor 2 / immunology
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Tumor Necrosis Factor-alpha / immunology
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Tumor Necrosis Factor-alpha / metabolism
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Up-Regulation / drug effects
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Up-Regulation / immunology
Substances
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Anti-Bacterial Agents
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Antigens, CD
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B7-1 Antigen
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B7-2 Antigen
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Histocompatibility Antigens Class II
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Immunoglobulins
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Immunologic Factors
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Membrane Glycoproteins
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Naphthoquinones
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Receptors, Interferon
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TLR2 protein, human
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Toll-Like Receptor 2
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Tumor Necrosis Factor-alpha
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Interleukin-10
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Interferon-gamma
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lapachol
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Nitrogen
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Oxygen