Abstract
Chemokines, including MCP-1, are crucial to mounting an effective immune response due to their ability to recruit other immune cells. We show that sustained LPS or poly(I:C)-stimulated MCP-1 production requires an IFNβ-mediated feedback loop. Consistent with this, exogenous IFNβ was able to induce MCP-1 transcription in the absence of other stimuli. Blocking IFNβ signaling with Ruxolitinib, a JAK inhibitor, inhibited MCP-1 transcription. The MCP-1 promoter contains potential STAT binding sites and we demonstrate that STAT1 is recruited upon IFNβ stimulation. Furthermore we find that IL-10 knockout increases MCP-1 production in response to LPS, which may reflect an ability of IL-10 to repress IFNβ production. Overall, these results show the importance of the balance between IFNβ and IL-10 in the regulation of MCP-1.
Copyright © 2013 Federation of European Biochemical Societies. Published by 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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Animals
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Autocrine Communication / drug effects
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Autocrine Communication / genetics
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Autocrine Communication / physiology*
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Cells, Cultured
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Chemokine CCL2 / genetics*
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Chemokine CCL2 / metabolism
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Feedback, Physiological / drug effects
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Feedback, Physiological / physiology*
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Interferon-beta / metabolism
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Interferon-beta / pharmacology
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Interferon-beta / physiology*
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Interleukin-10 / genetics
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Interleukin-10 / metabolism
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Interleukin-10 / physiology
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Macrophages / drug effects
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Macrophages / metabolism*
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Macrophages / physiology
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Receptor, Interferon alpha-beta / genetics
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Receptor, Interferon alpha-beta / metabolism
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Toll-Like Receptors / metabolism
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Toll-Like Receptors / physiology*
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Up-Regulation / drug effects
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Up-Regulation / genetics
Substances
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Ccl2 protein, mouse
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Chemokine CCL2
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Toll-Like Receptors
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Interleukin-10
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Receptor, Interferon alpha-beta
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Interferon-beta