title: IFNβ autocrine feedback is required to sustain TLR induced production of MCP-1 in macrophages.
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.
authors.affiliation: MRC Protein Phosphorylation Unit, Wellcome Trust Building, College of Life Sciences, University of Dundee, Dundee DD1 5EH, Scotland.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Pattison
authors.forename: Kirsty F
authors.initials: KF
authors.lastname: MacKenzie
authors.forename: Suzanne E
authors.initials: SE
authors.lastname: Elcombe
authors.forename: J Simon C
authors.initials: JS
authors.lastname: Arthur
mesh_terms: D000818:Animals; D019898:Autocrine Communication / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000235:genetics* / Q000378:metabolism; D025461:Feedback, Physiological / Q000187:drug effects / Q000502:physiology*; D016899:Interferon-beta / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D016753:Interleukin-10 / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053633:Receptor, Interferon alpha-beta / Q000235:genetics / Q000378:metabolism; D051193:Toll-Like Receptors / Q000378:metabolism / Q000502:physiology*; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics
chemical_list: C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D051193:Toll-Like Receptors; D016753:Interleukin-10; D053633:Receptor, Interferon alpha-beta; D016899:Interferon-beta
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