PMID:24317040

Citation	De Nardo, D, Labzin, LI, Kono, H, Seki, R, Schmidt, SV, Beyer, M, Xu, D, Zimmer, S, Lahrmann, C, Schildberg, FA, Vogelhuber, J, Kraut, M, Ulas, T, Kerksiek, A, Krebs, W, Bode, N, Grebe, A, Fitzgerald, ML, Hernandez, NJ, Williams, BR, Knolle, P, Kneilling, M, Röcken, M, Lütjohann, D, Wright, SD, Schultze, JL and Latz, E (2014) High-density lipoprotein mediates anti-inflammatory reprogramming of macrophages via the transcriptional regulator ATF3. Nat. Immunol. 15:152-60
Abstract	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.
Links	PubMed PMC4009731 Online version:10.1038/ni.2784
Keywords	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/therapy; Cells, Cultured; Cholesterol/metabolism; Chromatin Immunoprecipitation; Cytokines/secretion; Female; Gene Expression Profiling; High-Throughput Nucleotide Sequencing; Humans; Inflammation/therapy; Lipoproteins, HDL/pharmacology; Lipoproteins, HDL/therapeutic use; Macrophage Activation/drug effects; Macrophages/drug effects; Macrophages/immunology; Mice; Mice, Inbred C3H; Mice, Inbred C57BL; Systems Biology; Toll-Like Receptor 4/genetics; Toll-Like Receptor 4/immunology
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
MOUSE:Q3U4Z7		GO:0003723: RNA binding	ECO:0000314:		F		Figure 1 shows that HDL injected in mice with CpG DNA inhibits pro-inflammatory cytokines that cause liver damage by inducing cell death.	complete CACAO 10396

References

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