title: Effects of methotrexate on vascular endothelial growth factor, angiopoietin 1, and angiopoietin 2 in nasal polyps.
abstract: BACKGROUND
  Methotrexate (MTX) is a very effective treatment for chronic inflammatory diseases, which are often associated with increased angiogenesis. Angiogenesis is dependent on a perfectly coordinated balance between endogenous-positive and -negative regulatory factors, including vascular endothelial growth factor (VEGF) and the angiopoietins (Ang). The aim of this study was to investigate the effects of MTX on levels of VEGF, Ang-1, and Ang-2 in organ-cultured nasal polyps (NPs).
  
  
  METHODS
  To determine the effects of MTX, NP tissues were cultured using an air-liquid interface method. Cultures were maintained in the absence or presence of MTX (10 or 100 micromoles) for 24 hours. Hematoxylin and eosin, and TUNEL (terminal deoxynucleotidyl transferase [Tdt]-mediated dUTP-biotin nick-end labeling) staining were performed to observe apoptosis. Enzyme-linked immunosorbent assay was used to quantify tissue concentrations of VEGF, Ang-1, and Ang-2.
  
  
  RESULTS
  MTX treatment resulted in marked alterations in inflammatory cells, especially eosinophils. In contrast, the mucosal epithelium, microvessels including arterioles, veins and capillaries, and fibroblasts maintained their structure. TUNEL(+) cells (apoptotic cells) were seen in the MTX-treated specimens. The more induction of TUNEL(+) cells was observed 100-micromolar MTX-treated specimens. VEGF and Ang-1 levels were significantly lower, and Ang-2 levels were significantly higher in NPs treated with 100-micromolar MTX than in nontreated NPs (p < 0.01).
  
  
  CONCLUSIONS
  MTX may inhibit the growth of NPs via local regulation of VEGF, Ang-1, and Ang-2 protein levels. We suggest that MTX can be used to treat NPs.
authors.affiliation: Department of Otorhinolaryngology-Head and Neck Surgery, Inje University School of Medicine, Busan Paik Hospital, Busan, Korea. sinus4@paik.ac.kr
authors.forename: Seong Kook
authors.initials: SK
authors.lastname: Park
authors.forename: Hyeong In
authors.initials: HI
authors.lastname: Kim
authors.forename: Young Il
authors.initials: YI
authors.lastname: Yang
authors.forename: Dae Young
authors.initials: DY
authors.lastname: Hur
mesh_terms: D042683:Angiopoietin-1 / Q000235:genetics / Q000378:metabolism; D042702:Angiopoietin-2 / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D002908:Chronic Disease; D004797:Enzyme-Linked Immunosorbent Assay; D004804:Eosinophils / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D008727:Methotrexate / Q000494:pharmacology* / Q000627:therapeutic use; D009297:Nasal Mucosa / Q000473:pathology; D009298:Nasal Polyps; D009924:Organ Culture Techniques; D012220:Rhinitis / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D012852:Sinusitis / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
chemical_list: D042683:Angiopoietin-1; D042702:Angiopoietin-2; D042461:Vascular Endothelial Growth Factor A; D008727:Methotrexate