title: Recombinant human endostatin inhibits adjuvant arthritis by down-regulating VEGF expression and suppression of TNF-α, IL-1β production.
abstract: OBJECTIVE
  The aim of this study was to examine the effect of recombinant human endostatin (rhEndostatin) on adjuvant arthritis (AA) in rats and its possible mechanisms.
  
  
  METHODS
  RhEndostatin was subcutaneously administrated to AA rats after immunization. The progression of AA was assessed by the macroscopic arthritis scoring system of paws. Histological examination of the synovial tissues was examined by hematoxylin and eosin staining. The expression level of vascular endothelial growth factor (VEGF) mRNA and proteins in the synovial tissues was evaluated by realtime PCR and immunohistochemistry, respectively. Fibroblast-like synoviocytes (FLS) were isolated from synovial tissues. Cell proliferation assay was evaluateded with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide. The levels of tumour necrosis factor-alpha (TNF-α) and interleukin-1β (IL-1β) in culture medium was examined by radioimmno assay.
  
  
  RESULTS
  RhEndostatin attenuated the severity of arthritis on both second hind paw volume and polyarthritis score, as well as improved the arthritic status histologically in AA rats. Simultaneously, rhEndostatin can inhibit the expression of VEGF in synovial tissues. The proliferation of FLS and TNF-α, IL-1β production from culture medium was significantly inhibited by rhEndostatin.
  
  
  CONCLUSIONS
  Our data suggest that rhEndostatin inhibits adjuvant arthritis by down-regulating VEGF expression and suppression of TNF-α, IL-1β production.
authors.affiliation: Department of Pharmacology, College of Pharmacy, Anhui Medical University, Hefei, Anhui, People's Republic of China. huweiyf@163.com
authors.forename: Wei
authors.initials: W
authors.lastname: Hu
authors.forename: Li-Juan
authors.initials: LJ
authors.lastname: Xia
authors.forename: Fei-Hu
authors.initials: FH
authors.lastname: Chen
authors.forename: Fan-Rong
authors.initials: FR
authors.lastname: Wu
authors.forename: Jie
authors.initials: J
authors.lastname: Tang
authors.forename: Cun-Zhi
authors.initials: CZ
authors.lastname: Chen
authors.forename: Sheng
authors.initials: S
authors.lastname: Jiang
authors.forename: Hui-Hui
authors.initials: HH
authors.lastname: Chen
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D049109:Cell Proliferation; D002478:Cells, Cultured; D015536:Down-Regulation; D043169:Endostatins / Q000627:therapeutic use*; D006801:Humans; D053583:Interleukin-1beta / Q000378:metabolism*; D017746:Joint Capsule / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000627:therapeutic use*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
chemical_list: D043169:Endostatins; D053583:Interleukin-1beta; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat