Journal Article

High-density lipoprotein mediates anti-inflammatory reprogramming of macrophages via the transcriptional regulator ATF3

De Nardo, Dominic, Williams, Bryan R G, Schultze, Joachim L, Ulas, Thomas, Kneilling, Manfred, Röcken, Martin, Grebe, Alena, Knolle, Percy, Kerksiek, Anja, Krebs, Wolfgang, Hernandez, Nicholas J, Schildberg, Frank A, Beyer, Marc, Zimmer, Sebastian, Seki, Reiko, Fitzgerald, Michael L, Vogelhuber, Johanna, Bode, Niklas, Schmidt, Susanne V, Lahrmann, Catharina, Lütjohann, Dieter, Xu, Dakang, Kraut, Michael, Wright, Samuel D, Kono, Hajime, Labzin, Larisa I, Latz, Eicke

2014

Overview

High-density lipoprotein (HDL) has beneficial effects in coronary artery disease. Latz and colleagues show that HDL's benefits stem at least in part by activating an anti-inflammatory program dependent on the transcription factor ATF3. 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.

• Publisher: Nature Publishing Group US,Nature Publishing Group
• Subject: 631/250/256/2516 / 692/699/249/2510/2100 / Activating Transcription Factor 3 - genetics / Activating Transcription Factor 3 - metabolism / Animals / Anti-Inflammatory Agents, Non-Steroidal - pharmacology / Anti-Inflammatory Agents, Non-Steroidal - therapeutic use / Atherosclerosis / Atherosclerosis - therapy / Biomedicine / Care and treatment / Cells, Cultured / Cholesterol / Cholesterol - metabolism / Chromatin Immunoprecipitation / Cytokines - secretion / Female / Gene Expression Profiling / Genetic aspects / Health aspects / High density lipoproteins / High-Throughput Nucleotide Sequencing / Humans / Immunology / Infectious Diseases / Inflammation - therapy / Lipoproteins, HDL - pharmacology / Lipoproteins, HDL - therapeutic use / Macrophage Activation - drug effects / Macrophages / Macrophages - drug effects / Macrophages - immunology / Mice / Mice, Inbred C3H / Mice, Inbred C57BL / Physiological aspects / Systems Biology / Toll-Like Receptor 4 - genetics / Toll-Like Receptor 4 - immunology