title: Docosahexaenoic acid induces M2 macrophage polarization through peroxisome proliferator-activated receptor γ activation.
abstract: OBJECTIVE
  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.
  
  
  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 γ (PPARγ) in DHA-mediated effects, siRNA against PPARγ was utilized. The expression of PPARγ was examined by semiquantitative reverse-transcription polymerase chain reaction (RT-PCR), Western blot analysis and immunocytochemistry. The PPARγ activation was measured by the electrophilic gel shift assay.
  
  
  RESULTS
  DHA enhanced the efferocytic ability of RAW264.7 cells, and induced their M2 polarization. Notably, knockdown of PPARγ abolished the stimulatory effect of DHA on M2 polarization as well as efferocytosis. Furthermore, lipopolysaccharide-induced production of pro-inflammatory cytokines was significantly inhibited by DHA, suggesting that DHA alters the macrophage phenotype in favor of M2 while it suppresses M1 polarization.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Tumor Microenvironment Global Core Research Center, College of Pharmacy, Seoul National University, Seoul 151-742, South Korea.
authors.forename: Hae Yeun
authors.initials: HY
authors.lastname: Chang
authors.affiliation: Tumor Microenvironment Global Core Research Center, College of Pharmacy, Seoul National University, Seoul 151-742, South Korea.
authors.forename: Ha-Na
authors.initials: HN
authors.lastname: Lee
authors.affiliation: Tumor Microenvironment Global Core Research Center, College of Pharmacy, Seoul National University, Seoul 151-742, South Korea.
authors.forename: Wonki
authors.initials: W
authors.lastname: Kim
authors.affiliation: Tumor Microenvironment Global Core Research Center, College of Pharmacy, Seoul National University, Seoul 151-742, South Korea; Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul 151-742, South Korea; Cancer Research Institute, Seoul National University, Seoul 110-744, South Korea. Electronic address: surh@snu.ac.kr.
authors.forename: Young-Joon
authors.initials: YJ
authors.lastname: Surh
mesh_terms: D021581:Active Transport, Cell Nucleus; D000818:Animals; D017209:Apoptosis; D050197:Atherosclerosis / Q000503:physiopathology; D002460:Cell Line; D004281:Docosahexaenoic Acids / Q000737:chemistry*; D005786:Gene Expression Regulation; D006801:Humans; D007249:Inflammation; D019169:Jurkat Cells; D008264:Macrophages / Q000166:cytology / Q000187:drug effects*; D051379:Mice; D047495:PPAR gamma / Q000378:metabolism*; D010641:Phenotype; D034741:RNA, Small Interfering / Q000378:metabolism
chemical_list: D047495:PPAR gamma; D034741:RNA, Small Interfering; D004281:Docosahexaenoic Acids
keywords: Docosahexaenoic acid; Efferocytosis; Omega-3 polyunsaturated fatty acid; Peroxisome proliferator-activated receptor γ; Resolution of inflammation