Abstract
Toll-like receptor (TLR) signaling activation by pathogens is critical to the induction of immune responses, and demands tight regulation. We describe in this study that CC chemokine ligand 2 (CCL2) secretion triggered by TLR4 or TLR8 engagement is strongly inhibited upon simultaneous activation of both TLRs in human monocyte-derived dendritic cells (DCs). Impaired CCL2 secretion occurs concomitantly to interleukin-12 up-regulation, being part of a complex regulatory circuit ensuring optimal T helper type 1 polarization. Interestingly, triggering selected TLRs or their combinations differently affects nuclear factor-kappaB p65 activation and microRNA expression. Overall, these results indicate that CCL2 supplies an important immunomodulatory role to DCs, and may contribute to dictate the cytokine profile in T helper type 1 responses induced by DCs.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Cell Polarity / drug effects*
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Cells, Cultured
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Chemokine CCL2 / genetics
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Chemokine CCL2 / metabolism*
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Dendritic Cells / drug effects*
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Dendritic Cells / metabolism
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Down-Regulation / drug effects
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Drug Combinations
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Humans
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Imidazoles / administration & dosage
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Imidazoles / pharmacology
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Interferon-beta / metabolism
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Interleukin-10 / metabolism
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Lipopolysaccharides / administration & dosage
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Lipopolysaccharides / pharmacology
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Poly I-C / administration & dosage
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Poly I-C / pharmacology
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RNA, Messenger / metabolism
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Th1 Cells / drug effects*
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Th1 Cells / immunology
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Th1 Cells / metabolism
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Th1 Cells / physiology
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Toll-Like Receptors / agonists*
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Tumor Necrosis Factor-alpha / metabolism
Substances
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Chemokine CCL2
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Drug Combinations
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Imidazoles
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Lipopolysaccharides
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RNA, Messenger
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Toll-Like Receptors
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Tumor Necrosis Factor-alpha
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Interleukin-10
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Interferon-beta
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Poly I-C
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resiquimod