title: Suppression of type II collagen-induced arthritis by the endogenous estrogen metabolite 2-methoxyestradiol.
abstract: OBJECTIVE
  To evaluate the antiarthritic properties of 2-methoxyestradiol, an endogenous metabolite of estradiol, on type II collagen-induced arthritis (CIA) in DBA/1 mice.
  
  
  METHODS
  The effects of treatment with 2-methoxyestradiol on the development of CIA were evaluated clinically and histologically. The in vitro effects of 2-methoxyestradiol on lymphocyte and endothelial cell proliferation and differentiation were analyzed by standard methods.
  
  
  RESULTS
  The development of CIA was significantly suppressed by 2-methoxyestradiol. Incubation with 2-methoxyestradiol suppressed the in vitro proliferation of endothelial cells, indicating that this compound down-regulates angiogenesis. Endothelial cell production of nitric oxide (NO) was also down-regulated by 2-methoxyestradiol. In contrast to estradiol, 2-methoxyestradiol exerted neither detectable feminizing effects on the sex organs nor inhibition of leukocyte development in hematopoietic organs.
  
  
  CONCLUSIONS
  The development of CIA is suppressed by 2-methoxyestradiol, possibly via inhibition of angiogenesis. Diminished NO production could be of importance in vivo because it is a potent proinflammatory mediator. Since 2-methoxyestradiol exerts only mild side effects compared with estradiol, it is an interesting candidate for therapeutic use in inflammatory diseases.
authors.affiliation: University of Göteborg, Sweden.
authors.forename: E
authors.initials: E
authors.lastname: Josefsson
authors.forename: A
authors.initials: A
authors.lastname: Tarkowski
mesh_terms: D000077584:2-Methoxyestradiol; D000818:Animals; D001169:Arthritis, Experimental / Q000188:drug therapy*; D001835:Body Weight / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D003094:Collagen; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D004958:Estradiol / Q000031:analogs & derivatives* / Q000494:pharmacology; D005260:Female; D006066:Gonads / Q000187:drug effects; D007249:Inflammation / Q000188:drug therapy; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis / Q000187:drug effects; D007596:Joints / Q000187:drug effects* / Q000473:pathology; D007962:Leukocytes / Q000187:drug effects; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D009569:Nitric Oxide / Q000378:metabolism
chemical_list: D018799:Intercellular Adhesion Molecule-1; D009569:Nitric Oxide; D004958:Estradiol; D000077584:2-Methoxyestradiol; D003094:Collagen