title: Sesamin suppresses macrophage-derived chemokine expression in human monocytes via epigenetic regulation.
abstract: BACKGROUND
  Chemokines play important roles in the pathogenesis of asthmatic inflammation. Sesamin, a class of phytoestrogen isolated from sesame seed Sesamum indicum, is recently regarded as an anti-inflammatory agent. However, the effects of sesamin on asthma-related chemokines are unknown. To this end, we investigated the effects of sesamin on the expression interferon-γ-inducible protein-10 (IP-10/CXCL10), macrophage-derived chemokine (MDC/CCL22), growth-related oncogene-α (GRO-α/CXCL1) and tumor necrosis factor (TNF)-α in human monocytes.
  
  
  METHODS
  Cells were pretreated with sesamin before lipopolysaccharide (LPS) stimulation. IP-10, MDC, GRO-α and TNF-α were measured by ELISA. Involved receptors and intracellular signaling were investigated by receptor antagonists, pathway inhibitors, western blotting and chromatin immunoprecipitation.
  
  
  RESULTS
  Sesamin suppressed LPS-induced MDC in THP-1 and human primary monocytes. Sesamin suppressed LPS-induced IP-10 in THP-1 cells, but not human primary monocytes. Sesamin had no effects on LPS-induced GRO-α and TNF-α expression in THP-1 and human primary monocytes. The suppressive effect of sesamin on MDC was reversed by the estrogen receptor (ER) and peroxisomal proliferator-activated receptor (PPAR)-α antagonists. Sesamin suppressed LPS-induced phosphorylation of mitogen-activated protein kinase (MAPK)-p38 and nuclear factor kappa B (NFκB)-p65. Sesamin suppressed histone H3/H4 acetylation in the MDC promoter region.
  
  
  CONCLUSIONS
  Sesamin suppressed LPS-induced MDC expression via the ER, the PPAR-α, the MAPK-p38 pathway, the NFκB-p65 pathway and the epigenetic regulation. Sesamin may have therapeutic potential in preventing and treating asthma.
authors.affiliation: Division of Cardiovascular Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
authors.forename: Chong-Chao
authors.initials: CC
authors.lastname: Hsieh
authors.forename: Chang-Hung
authors.initials: CH
authors.lastname: Kuo
authors.forename: Hsuan-Fu
authors.initials: HF
authors.lastname: Kuo
authors.forename: Yen-Shan
authors.initials: YS
authors.lastname: Chen
authors.forename: Shih-Ling
authors.initials: SL
authors.lastname: Wang
authors.forename: David
authors.initials: D
authors.lastname: Chao
authors.forename: Min-Sheng
authors.initials: MS
authors.lastname: Lee
authors.forename: Chih-Hsing
authors.initials: CH
authors.lastname: Hung
mesh_terms: D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001249:Asthma / Q000188:drug therapy; D045744:Cell Line, Tumor; D054422:Chemokine CCL22 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D054360:Chemokine CXCL1 / Q000235:genetics / Q000378:metabolism; D054357:Chemokine CXCL10 / Q000235:genetics / Q000378:metabolism; D004149:Dioxoles / Q000494:pharmacology*; D044127:Epigenesis, Genetic; D006657:Histones / Q000235:genetics / Q000378:metabolism; D006801:Humans; D017705:Lignans / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000009:adverse effects; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism; D047493:PPAR alpha / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D011401:Promoter Regions, Genetic; D011960:Receptors, Estrogen / Q000235:genetics / Q000378:metabolism; D012639:Seeds / Q000737:chemistry; D031685:Sesamum / Q000737:chemistry; D015398:Signal Transduction; D051996:Transcription Factor RelA / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; C515482:CCL22 protein, human; C475829:CXCL1 protein, human; C114753:CXCL10 protein, human; D054422:Chemokine CCL22; D054360:Chemokine CXCL1; D054357:Chemokine CXCL10; D004149:Dioxoles; D006657:Histones; D017705:Lignans; D008070:Lipopolysaccharides; D047493:PPAR alpha; C498143:RELA protein, human; D011960:Receptors, Estrogen; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; D048051:p38 Mitogen-Activated Protein Kinases; C054125:sesamin