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IFNβ autocrine feedback is required to sustain TLR induced production of MCP‐1 in macrophages
Author(s) -
Pattison Michael J.,
MacKenzie Kirsty F.,
Elcombe Suzanne E.,
Arthur J. Simon C.
Publication year - 2013
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2013.03.025
Subject(s) - stat1 , autocrine signalling , chemokine , stat , microbiology and biotechnology , transcription (linguistics) , immune system , stimulation , chemistry , interferon , stat3 , signal transduction , biology , immunology , receptor , biochemistry , neuroscience , linguistics , philosophy
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.