title: Interleukin-1 receptor antagonist intervenes in signaling between different types of synoviocytes in rats with adjuvant arthritis.
abstract: OBJECTIVE
  To investigate the mechanisms of interleukin-1 receptor antagonist (IL-1ra) in the treatment of adjuvant arthritis (AA).
  
  
  METHODS
  AA was induced in rats by treatment with Freunds complete adjuvant (FCA). Rats were given an intracutaneous injection of IL-1ra (2.5, 10, 40 mg/kg, 3 times per day) from d 14 to d 21 after immunization. Synoviocyte proliferation and the activity of IL-1 were determined by using MTT assay. Tumor necrosis factor alpha (TNF-alpha) and prostaglandin E(2) (PGE(2)) concentrations were measured by radioimmunoassay. The ultrastructure of synoviocytes was observed by using a transmission electron microscope. Phosphorylation of c-Jun N-terminal kinase (JNK), extracellular regulating kinase (ERK) and p38 kinase were detected by Western blot analysis.
  
  
  RESULTS
  IL-1ra (10 and 40 mg/kg, ic, d 14-21) modulated the secondary inflammatory reaction (P < 0.01), ultrastructure of synoviocytes and mitogen-activated protein kinase (MAPK) phosphorylation in AA rats. The administration of IL-1ra (10 and 40 mg/kg, ic, d 14-21) in AA rats significantly decreased the production of IL-1, PGE2 and TNF-alpha by macrophage-like synoviocytes (MLS) (P < 0.01). IL-1ra (2.5 mg/kg) also decreased the production of PGE2 (P < 0.01) and TNF-alpha (P < 0.05) by MLS in AA rats. The increased phosphorylation of MAPK and cell proliferation in fibroblast-like synoviocytes (FLS) stimulated by supernatants of MLS in AA rats was also inhibited by IL-1ra (10 and 40 mg/kg, ic, d 14-21).
  
  
  CONCLUSIONS
  IL-1ra has anti-inflammatory effects because it modulates the ultrastructure of synoviocytes, decreases the production of pro-inflammatory mediators by MLS, and inhibits the phosphorylation of MAPK in FLS.
authors.affiliation: Institute of Clinical Pharmacology, Anhui Medical University, Hefei, China.
authors.forename: Yong-qiu
authors.initials: YQ
authors.lastname: Zheng
authors.forename: Wei
authors.initials: W
authors.lastname: Wei
authors.forename: Min
authors.initials: M
authors.lastname: Dai
authors.forename: Lei
authors.initials: L
authors.lastname: Zhu
authors.forename: Xiao-yi
authors.initials: XY
authors.lastname: Jia
authors.forename: Yuan
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D015232:Dinoprostone / Q000378:metabolism; D005620:Freund's Adjuvant; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000378:metabolism; D008297:Male; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism*; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors; D012795:Sialoglycoproteins / Q000494:pharmacology*; D013583:Synovial Membrane / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D017472:Receptors, Interleukin-1; D012795:Sialoglycoproteins; D014409:Tumor Necrosis Factor-alpha; D005620:Freund's Adjuvant; D020929:Mitogen-Activated Protein Kinase Kinases; D015232:Dinoprostone