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Docosahexaenoic acid induces M2 macrophage polarization through peroxisome proliferator-activated receptor gamma activation

Cited 55 time in Web of Science Cited 59 time in Scopus
Authors
Chang, Hae Yeun; Lee, Ha-Na; Kim, Wonki; Surh, Young-Joon
Issue Date
2015-01
Citation
Life Sciences, Vol.120, pp.39-47
Keywords
Docosahexaenoic acidEfferocytosisResolution of inflammationOmega-3 polyunsaturated fatty addPeroxisome proliferator-activated receptor gamma
Abstract
Aims: Impaired resolution of acute inflammation results in development of chronic inflammatory disorders such as atherosclerosis, asthma and arthritis. Clearance of apoptotic neutrophils by M2 macrophages, the process termed efferocytosis, is critical for complete resolution of inflammation as it prevents secondary necrosis caused by disgorgement of toxic contents from apoptotic cells in the inflamed site. In the present study, we investigated the effect of docosahexaenoic acid (DHA) on efferocytosis. Main methods: To determine the effect of DHA on efferocytosis, murine macrophage-like RAW264.7 cells were co-incubated with apoptotic Jurkat T cells, and efferocytosis was assessed by flow cytometry. The expression and production of M1 and M2 markers were determined by RT-PCR, ELISA and flow cytometry. To demonstrate the involvement of peroxisome proliferator-activated receptor 'y (PPARy) in DHA-mediated effects, siRNA against PPARy was utilized. The expression of PPAR'y was examined by semiquantitative reverse-transcription polymerase chain reaction (RT-PCR), Western blot analysis and immunocytochemistry. The [TAR)/ activation was measured by the electrophilic gel shift assay. Key findings: DHA enhanced the efferocytic ability of RAW264.7 cells, and induced their M2 polarization. Notably, knockdown of PPARy abolished the stimulatory effect of DHA on M2 polarization as well as efferocytosis. Furthermore, lipopcilysaccharide-induced production of pro-inflammatory cytoldnes was significantly inhibited by DHA, suggesting that DI-IA alters the macrophage phenotype in favor of M2 while it suppresses M1 polarization. Significance: These findings indicate that DHA can promote resolution of inflammation by facilitating efferocytosis through M2 macrophage polarization. Therefore, DHA may have a therapeutic potential in the management of inflammatory diseases which are related to impaired resolution of inflammation. 0 2014 Elsevier Inc. All rights reserved.
ISSN
0024-3205
URI
https://hdl.handle.net/10371/172810
DOI
https://doi.org/10.1016/j.lfs.2014.10.014
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Graduate School of Convergence Science and Technology (융합과학기술대학원)Dept. of Molecular and Biopharmaceutical Sciences (분자의학 및 바이오제약학과)Journal Papers (저널논문_분자의학 및 바이오제약학과)
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