title: Pyropia yezoensis glycoprotein promotes the M1 to M2 macrophage phenotypic switch via the STAT3 and STAT6 transcription factors.
abstract: Macrophage polarization has been well documented. Macrophages can aquire two phenotypes, the pro-inflammatory M1 phenotype, and the anti-inflammatory and wound healing M2 phenotype. The M1 macrophage phenotype has been linked to metabolic disease and is also associated with cancer-related inflammation. Of note, macrophage polarization can be influenced by the extracellular environment. In the current study, we examined the effects of Pyropia yezoensis glycoprotein (PYGP) on M1 to M2 macrophage polarization in lipopolysaccharide (LPS)-stimulated macrophages. RAW 264.7 macrophages stimulated with LPS exhibited an upregulated expression of pro-inflammatory mediators, namely of the M1 markers, nitric oxide (NO), reactive oxygen species (ROS), interleukin (IL)-6, IL-1β, tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ) and nitric oxide synthase‑2 (NOS-2). Treatment with PYGP inhibited the production of M1 markers and increased arginase 1 (ARG1), chitinase-like 3 (Chil3; also known as Ym1), resistin like beta (RETNLB; also known as FIZZ1), IL-10, CD163, CD206, peroxisome proliferator-activated receptor γ (PPARγ) and Krüppel-like factor 4 (KLF4) M2 marker gene expression. The signal transducer and activator of transcription (STAT)3 and STAT6 transcription factors were phosphorylated following treatment with PYGP. However, the silencing of STAT3 and STAT6 using siRNA in the macrophages decreased ARG1, Ym1 and FIZZ1 M2 marker gene expression in spite of treatment of PYGP. These findings suggest that PYGP exerts anti-inflammatory effects by regulating the M1 to M2 phenotypic switch through STAT3 and STAT6. Thus, PYGP may have potential for use as a natural remedy for inflammatory diseases.
authors.affiliation: Department of Food and Life Science, Pukyong National University, Busan 608-737, Republic of Korea.
authors.forename: Jeong-Wook
authors.initials: JW
authors.lastname: Choi
authors.affiliation: Institute of Fisheries Science, Pukyong National University, Busan 619-911, Republic of Korea.
authors.forename: Mi-Jin
authors.initials: MJ
authors.lastname: Kwon
authors.affiliation: Institute of Fisheries Science, Pukyong National University, Busan 619-911, Republic of Korea.
authors.forename: In-Hye
authors.initials: IH
authors.lastname: Kim
authors.affiliation: Department of Food and Life Science, Pukyong National University, Busan 608-737, Republic of Korea.
authors.forename: Young-Min
authors.initials: YM
authors.lastname: Kim
authors.affiliation: Department of Food and Life Science, Pukyong National University, Busan 608-737, Republic of Korea.
authors.forename: Min-Kyeong
authors.initials: MK
authors.lastname: Lee
authors.affiliation: Department of Food and Life Science, Pukyong National University, Busan 608-737, Republic of Korea.
authors.forename: Taek-Jeong
authors.initials: TJ
authors.lastname: Nam
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D016764:Cell Polarity / Q000187:drug effects*; D015232:Dinoprostone / Q000096:biosynthesis; D006023:Glycoproteins / Q000494:pharmacology*; D000090062:Kruppel-Like Factor 4; D008070:Lipopolysaccharides; D008262:Macrophage Activation / Q000187:drug effects; D008264:Macrophages / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D009569:Nitric Oxide / Q000378:metabolism; D010641:Phenotype; D000067996:RAW 264.7 Cells; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D000461:Rhodophyta / Q000737:chemistry*; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D050800:STAT6 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D014162:Transfection
chemical_list: D015415:Biomarkers; D006023:Glycoproteins; C000715468:Klf4 protein, mouse; D000090062:Kruppel-Like Factor 4; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; D050796:STAT3 Transcription Factor; D050800:STAT6 Transcription Factor; D017392:Thiobarbituric Acid Reactive Substances; D009569:Nitric Oxide; D015232:Dinoprostone