TY - JOUR
T1 - IFNβ autocrine feedback is required to sustain TLR induced production of MCP-1 in macrophages
AU - Pattison, Michael J.
AU - MacKenzie, Kirsty F.
AU - Elcombe, Suzanne E.
AU - Arthur, J. Simon C.
N1 - Copyright 2013 Elsevier B.V., All rights reserved.
PY - 2013/5/21
Y1 - 2013/5/21
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84875925924&partnerID=8YFLogxK
U2 - 10.1016/j.febslet.2013.03.025
DO - 10.1016/j.febslet.2013.03.025
M3 - Article
C2 - 23542035
SN - 0014-5793
VL - 587
SP - 1496
EP - 1503
JO - FEBS Letters
JF - FEBS Letters
IS - 10
ER -