title: HDL induces the expression of the M2 macrophage markers arginase 1 and Fizz-1 in a STAT6-dependent process.
abstract: Our lab has previously shown in a mouse model that normalization of a low HDL level achieves atherosclerotic plaque regression. This included the shift from a pro ("M1") to an anti-inflammatory ("M2") phenotypic state of plaque macrophages. Whether HDL can directly cause this phenotypic change and, if so, what the signaling mechanism is, were explored in the present studies. Murine primary macrophages treated with HDL showed increased gene expression for the M2 markers Arginase-1 (Arg-1) and Fizz-1, which are classically induced by IL-4. HDL was able to potentiate the IL-4-induced changes in Arg-1, and tended to do the same for Fizz-1, while suppressing the expression of inflammatory genes in response to IFNγ. The effects of either IL-4 or HDL were suppressed when macrophages were from STAT6(-/-) mice, but inhibitor studies suggested differential utilization of JAK isoforms by IL-4 and HDL to activate STAT6 by phosphorylation. Overall, our results describe a new function of HDL, namely its ability to directly enrich macrophages in markers of the M2, anti-inflammatory, state in a process requiring STAT6.
authors.affiliation: The Leon H. Charney Division of Cardiology and Marc and Ruti Bell Program in Vascular Biology, Department of Medicine, New York University School of Medicine, New York, New York, USA.
authors.forename: Marie
authors.initials: M
authors.lastname: Sanson
authors.forename: Emilie
authors.initials: E
authors.lastname: Distel
authors.forename: Edward A
authors.initials: EA
authors.lastname: Fisher
mesh_terms: D000818:Animals; D001119:Arginase / Q000378:metabolism*; D001483:Base Sequence; D015415:Biomarkers / Q000378:metabolism*; D017931:DNA Primers; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D015847:Interleukin-4 / Q000502:physiology; D008075:Lipoproteins, HDL / Q000502:physiology*; D008264:Macrophages / Q000166:cytology / Q000201:enzymology / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D010766:Phosphorylation; D016133:Polymerase Chain Reaction; D050796:STAT3 Transcription Factor / Q000378:metabolism; D050800:STAT6 Transcription Factor / Q000378:metabolism / Q000502:physiology*
chemical_list: D015415:Biomarkers; D017931:DNA Primers; D036341:Intercellular Signaling Peptides and Proteins; D008075:Lipoproteins, HDL; C413576:Retnla protein, mouse; D050796:STAT3 Transcription Factor; D050800:STAT6 Transcription Factor; C494087:Stat3 protein, mouse; C494100:Stat6 protein, mouse; D015847:Interleukin-4; C544448:Arg1 protein, mouse; D001119:Arginase