TY - JOUR
T1 - High-density lipoprotein mediates anti-inflammatory reprogramming of macrophages via the transcriptional regulator ATF3
AU - De Nardo, Dominic
AU - Labzin, Larisa I.
AU - Kono, Hajime
AU - Seki, Reiko
AU - Schmidt, Susanne V.
AU - Beyer, Marc
AU - Xu, Dakang
AU - Zimmer, Sebastian
AU - Lahrmann, Catharina
AU - Schildberg, Frank A.
AU - Vogelhuber, Johanna
AU - Kraut, Michael
AU - Ulas, Thomas
AU - Kerksiek, Anja
AU - Krebs, Wolfgang
AU - Bode, Niklas
AU - Grebe, Alena
AU - Fitzgerald, Michael L.
AU - Hernandez, Nicholas J.
AU - Williams, Bryan R.G.
AU - Knolle, Percy
AU - Kneilling, Manfred
AU - Röcken, Martin
AU - Lütjohann, Dieter
AU - Wright, Samuel D.
AU - Schultze, Joachim L.
AU - Latz, Eicke
N1 - Funding Information:
We acknowledge C. Thiele (University of Bonn) for helpful discussions and J.-C. Hernandez (University of Medellin) for help with experiments. We thank C.M. De Nardo for critical reading of the manuscript. We thank T. Hai (Ohio State University) for the original Atf3-deficient mice. The work was funded by grants from US National Institutes of Health (1R01HL093262 to E.L., and 1R01HL112661 to E.L. and M.L.F.), the German Research foundation (SFB670 to E.L., SFB685 to M.Kn. and M.R.), the Excellence Cluster ImmunoSensation to E.L. and J.L.S., the Australian National Health and Medical Research Council (1006588), the Operational Infrastructure Support Program (Victoria state Government, Australia) to B.R.G.W. and D.X., and the Naito Foundation (Japan) and the Ministry of Health, Labour and Welfare and Grant-in-Aid for Scientific Research on Innovative Areas for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan to H.K. E.L. is a member of the Center for Molecular Inflammation Research at the Norwegian University of Science and Technology.
PY - 2014/2
Y1 - 2014/2
N2 - High-density lipoprotein (HDL) mediates reverse cholesterol transport and is known to be protective against atherosclerosis. In addition, HDL has potent anti-inflammatory properties that may be critical for protection against other inflammatory diseases. The molecular mechanisms of how HDL can modulate inflammation, particularly in immune cells such as macrophages, remain poorly understood. Here we identify the transcriptional regulator ATF3, as an HDL-inducible target gene in macrophages that downregulates the expression of Toll-like receptor (TLR)-induced proinflammatory cytokines. The protective effects of HDL against TLR-induced inflammation were fully dependent on ATF3 in vitro and in vivo. Our findings may explain the broad anti-inflammatory and metabolic actions of HDL and provide the basis for predicting the success of new HDL-based therapies.
AB - High-density lipoprotein (HDL) mediates reverse cholesterol transport and is known to be protective against atherosclerosis. In addition, HDL has potent anti-inflammatory properties that may be critical for protection against other inflammatory diseases. The molecular mechanisms of how HDL can modulate inflammation, particularly in immune cells such as macrophages, remain poorly understood. Here we identify the transcriptional regulator ATF3, as an HDL-inducible target gene in macrophages that downregulates the expression of Toll-like receptor (TLR)-induced proinflammatory cytokines. The protective effects of HDL against TLR-induced inflammation were fully dependent on ATF3 in vitro and in vivo. Our findings may explain the broad anti-inflammatory and metabolic actions of HDL and provide the basis for predicting the success of new HDL-based therapies.
UR - http://www.scopus.com/inward/record.url?scp=84892737895&partnerID=8YFLogxK
U2 - 10.1038/ni.2784
DO - 10.1038/ni.2784
M3 - Article
C2 - 24317040
AN - SCOPUS:84892737895
SN - 1529-2908
VL - 15
SP - 152
EP - 160
JO - Nature Immunology
JF - Nature Immunology
IS - 2
ER -