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

Autor:	Nicholas J. Hernandez, Bryan R.G. Williams, Manfred Kneilling, Larisa I. Labzin, Susanne Schmidt, Sebastian Zimmer, Martin Röcken, Anja Kerksiek, Thomas Ulas, Reiko Seki, Michael L. Fitzgerald, Joachim L. Schultze, Samuel D. Wright, Michael Kraut, Dominic De Nardo, Alena Grebe, Dakang Xu, Catharina Lahrmann, Dieter Lütjohann, Marc Beyer, Percy A. Knolle, Wolfgang Krebs, Niklas Bode, Frank A. Schildberg, Hajime Kono, Johanna Vogelhuber, Eicke Latz
Rok vydání:	2013
Předmět:	030204 cardiovascular system & hematology Mice chemistry.chemical_compound 0302 clinical medicine High-density lipoprotein therapy [Atherosclerosis] Transcriptional regulation Immunology and Allergy genetics [Activating Transcription Factor 3] Cells Cultured therapeutic use [Anti-Inflammatory Agents Non-Steroidal] drug effects [Macrophages] Mice Inbred C3H 0303 health sciences Systems Biology Anti-Inflammatory Agents Non-Steroidal Reverse cholesterol transport immunology [Toll-Like Receptor 4] High-Throughput Nucleotide Sequencing immunology [Macrophages] 3. Good health Cell biology Cholesterol Cytokines Female lipids (amino acids peptides and proteins) medicine.symptom Lipoproteins HDL Chromatin Immunoprecipitation Immunology Inflammation Biology metabolism [Activating Transcription Factor 3] Proinflammatory cytokine pharmacology [Anti-Inflammatory Agents Non-Steroidal] 03 medical and health sciences Immune system therapy [Inflammation] medicine Animals Humans pharmacology [Lipoproteins HDL] drug effects [Macrophage Activation] ddc:610 030304 developmental biology Activating Transcription Factor 3 Gene Expression Profiling metabolism [Cytokines] nutritional and metabolic diseases genetics [Toll-Like Receptor 4] metabolism [Cholesterol] Mice Inbred C57BL Toll-Like Receptor 4 chemistry Atf3 protein mouse therapeutic use [Lipoproteins HDL] Lipoprotein
Zdroj:	Nature immunology 15(2), 152-160 (2013). doi:10.1038/ni.2784
ISSN:	1529-2916 1529-2908
Popis:	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.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::fa4432d568758586446f7f0f1fbaec5f https://doi.org/10.1038/ni.2784 Zobrazit plný text záznamu