IFNβ autocrine feedback is required to sustain TLR induced production of MCP-1 in macrophages

Michael J. Pattison, Kirsty F. MacKenzie, Suzanne E. Elcombe, J. Simon C. Arthur

    Research output: Contribution to journalArticlepeer-review

    17 Citations (Scopus)

    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 IFNß-mediated feedback loop. Consistent with this, exogenous IFNß was able to induce MCP-1 transcription in the absence of other stimuli. Blocking IFNß 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 IFNß 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 IFNß production. Overall, these results show the importance of the balance between IFNß and IL-10 in the regulation of MCP-1.
    Original languageEnglish
    Pages (from-to)1496-1503
    Number of pages8
    JournalFEBS Letters
    Volume587
    Issue number10
    Early online date28 Mar 2013
    DOIs
    Publication statusPublished - 21 May 2013

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