title: Estrogen receptor β agonist diarylpropionitrile inhibits lipopolysaccharide-induced regulated on activation normal T cell expressed and secreted (RANTES) production in macrophages by repressing nuclear factor κB activation.
abstract: OBJECTIVE
  To investigate the effect of the estrogen receptor-β (ERβ) agonist diarylpropionitrile (DPN) on lipopolysaccharide (LPS)-induced regulated on activation normal T cell expressed and secreted (RANTES) production in macrophages and the possible mechanisms.
  
  
  METHODS
  Cellular and molecular biology experimental study.
  
  
  METHODS
  University-based research laboratory.
  
  
  METHODS
  None.
  
  
  METHODS
  ERβ mRNA and protein expression determined in murine macrophage cell line RAW264.7 cells using reverse-transcription polymerase chain reaction and Western blot analysis; RANTES production detected by ELISA in LPS-stimulated RAW264.7 cells and ERβ knockdown RAW264.7 cells after the addition of DPN, phosphorylation of p65 and IκB degradation detected by Western blot analysis; and nuclear accumulation of p65 visualized using immunofluorescence.
  
  
  METHODS
  LPS-induced RANTES production and phosphorylation of p65 and IκB.
  
  
  RESULTS
  ERβ was expressed in RAW264.7 cells, and DPN statistically significantly decreased LPS-induced RANTES production in RAW264.7 cells. Small interfering RNA targeting the ERβ gene inhibited the effect of DPN on RANTES production. In addition, DPN inhibited nuclear translocation and phosphorylation of p65 by inhibiting IκB degradation and thus prohibited the activation of nuclear factor κB (NF-κB).
  
  
  CONCLUSIONS
  Diarylpropionitrile down-regulates LPS-induced RANTES production via ERβ. This effect of DPN is likely due to repression of nuclear factor κB activation.
authors.affiliation: Department of Pharmacology, School of Pharmacy, Fudan University, Shanghai, People's Republic of China.
authors.forename: Shi-ying
authors.initials: SY
authors.lastname: Huang
authors.forename: Hong
authors.initials: H
authors.lastname: Xin
authors.forename: Jing
authors.initials: J
authors.lastname: Sun
authors.forename: Rui
authors.initials: R
authors.lastname: Li
authors.forename: Xue-mei
authors.initials: XM
authors.lastname: Zhang
authors.forename: Dong
authors.initials: D
authors.lastname: Zhao
mesh_terms: D000818:Animals; D002460:Cell Line; D018946:Chemokine CCL5 / Q000096:biosynthesis* / Q000378:metabolism; D047629:Estrogen Receptor beta / Q000819:agonists* / Q000502:physiology; D005260:Female; D005786:Gene Expression Regulation; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors / Q000633:toxicity; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009570:Nitriles / Q000494:pharmacology*; D011422:Propionates / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism*
chemical_list: C486182:2,3-bis(4-hydroxyphenyl)-propionitrile; C503460:Ccl5 protein, mouse; D018946:Chemokine CCL5; D047629:Estrogen Receptor beta; D008070:Lipopolysaccharides; D016328:NF-kappa B; D009570:Nitriles; D011422:Propionates