Abstract
Though lactoferrin (LF) is a glycoprotein that is involved in immunomodulation, its action mechanism has not been fully elucidated. Previous studies have suggested that lipopolysaccharide (LPS) activity is inhibited by direct binding between LPS and LF. However, here we show that when LPS and purified LF was mixed, and formed a complex (termed as LF-LPS), it was found to induce production of inflammatory mediators in macrophages to some extent, rather than inhibit LPS activity. Moreover, when macrophages were pretreated with LF-LPS, cells were rendered a tolerant state to LPS challenge. These macrophage-activating effects were mediated by Toll-like receptor 4 (TLR4)-NF-kappaB pathway. Comparative studies with C3H/HeN and C3H/HeJ mice demonstrated the strong dependency of the LF-LPS signal on TLR4. These findings suggest that the immunomodulatory properties of LF could be due, in part, to LPS binding.
MeSH terms
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Acute-Phase Proteins / pharmacology*
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Animals
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Blotting, Western
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Carrier Proteins / pharmacology*
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Cells, Cultured
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Electrophoretic Mobility Shift Assay
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Immunoassay
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Inflammation / pathology*
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Lactoferrin / pharmacology*
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Lipopolysaccharides / pharmacology
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Macrophage Activation / drug effects*
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Membrane Glycoproteins / drug effects
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Membrane Glycoproteins / metabolism
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Membrane Glycoproteins / pharmacology*
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Mice
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Mice, Inbred C3H
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NF-kappa B / metabolism
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Nitrites / analysis
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Nitrites / metabolism
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Receptors, Cell Surface / drug effects
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Receptors, Cell Surface / metabolism
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Reverse Transcriptase Polymerase Chain Reaction
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Signal Transduction / drug effects
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Toll-Like Receptor 4
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Toll-Like Receptors
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Tumor Necrosis Factor-alpha / biosynthesis
Substances
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Acute-Phase Proteins
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Carrier Proteins
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Lipopolysaccharides
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Membrane Glycoproteins
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NF-kappa B
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Nitrites
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Receptors, Cell Surface
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Toll-Like Receptor 4
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Toll-Like Receptors
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Tumor Necrosis Factor-alpha
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lipopolysaccharide-binding protein
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Lactoferrin