title: Interleukin-17 receptor deficiency results in impaired synovial expression of interleukin-1 and matrix metalloproteinases 3, 9, and 13 and prevents cartilage destruction during chronic reactivated streptococcal cell wall-induced arthritis.
abstract: OBJECTIVE
  To examine the role of interleukin-17 receptor (IL-17R) signaling in cartilage destruction and its interrelationship with synovial IL-1 expression during chronic reactivated streptococcal cell wall (SCW)-induced arthritis.
  
  
  METHODS
  SCW arthritis was repeatedly induced in wild-type (WT) and IL-17R-deficient (IL-17R-/-) mice. At different time points, joint inflammation was assessed by using calipers to measure joint swelling. On day 42, mice were killed, and knee joints were removed for histologic analysis. Quantitative polymerase chain reaction (PCR) analyses for different proinflammatory mediators and matrix metalloproteinases (MMPs) were performed on inflamed synovium from WT and IL-17R-/- mice after 5 repeated injections of SCW fragments.
  
  
  RESULTS
  IL-17R signaling did not play a significant role in acute joint swelling induced by a single injection of SCW fragments directly into the joint. However, repeated local injections of SCW fragments into the knee joints of IL-17R-/- mice resulted in fewer infiltrating cells in the joint compared with WT mice. Moreover, histologic analysis on day 42 revealed a significant suppression of the degree of chondrocyte death and an absence of cartilage surface erosion in IL-17R-/- mice. Quantitative PCR analysis revealed impaired synovial expression of IL-1, IL-6, cyclooxygenase 2, stromelysin (MMP-3), gelatinase B (MMP-9), and collagenase 3 (MMP-13) in IL-17R-/- mice.
  
  
  CONCLUSIONS
  These data show a critical role of IL-17R signaling in driving the synovial expression of proinflammatory and catabolic mediators, such as IL-1 and different MMPs, during progression from an acute, macrophage-driven joint inflammation to a chronic, cartilage-destructive, T cell-mediated synovitis. Prevention of IL-17R signaling warrants consideration as a therapeutic target in chronic destructive arthritis.
authors.affiliation: University Medical Center St. Radboud, Nijmegen, The Netherlands.
authors.forename: Marije I
authors.initials: MI
authors.lastname: Koenders
authors.forename: Jay K
authors.initials: JK
authors.lastname: Kolls
authors.forename: Birgitte
authors.initials: B
authors.lastname: Oppers-Walgreen
authors.forename: Liduine
authors.initials: L
authors.lastname: van den Bersselaar
authors.forename: Leo A B
authors.initials: LA
authors.lastname: Joosten
authors.forename: Jill R
authors.initials: JR
authors.lastname: Schurr
authors.forename: Paul
authors.initials: P
authors.lastname: Schwarzenberger
authors.forename: Wim B
authors.initials: WB
authors.lastname: van den Berg
authors.forename: Erik
authors.initials: E
authors.lastname: Lubberts
mesh_terms: D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism; D001169:Arthritis, Experimental / Q000276:immunology / Q000473:pathology* / Q000503:physiopathology*; D002356:Cartilage / Q000201:enzymology / Q000276:immunology / Q000473:pathology; D016923:Cell Death; D019902:Chondrocytes / Q000473:pathology / Q000502:physiology; D002908:Chronic Disease; D017364:Collagenases / Q000235:genetics; D004195:Disease Models, Animal; D005260:Female; D007375:Interleukin-1 / Q000235:genetics*; D020381:Interleukin-17 / Q000235:genetics*; D008297:Male; D053509:Matrix Metalloproteinase 13; D019278:Matrix Metalloproteinase 3 / Q000235:genetics; D020780:Matrix Metalloproteinase 9 / Q000235:genetics; D020782:Matrix Metalloproteinases / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D012333:RNA, Messenger / Q000032:analysis; D015398:Signal Transduction / Q000276:immunology; D013047:Specific Pathogen-Free Organisms; D013291:Streptococcus / Q000276:immunology; D013583:Synovial Membrane / Q000201:enzymology / Q000276:immunology / Q000473:pathology
chemical_list: D000945:Antigens, Differentiation, T-Lymphocyte; C098680:Il17a protein, mouse; D007375:Interleukin-1; D020381:Interleukin-17; D012333:RNA, Messenger; D017364:Collagenases; D053509:Matrix Metalloproteinase 13; D020782:Matrix Metalloproteinases; C507081:Mmp13 protein, mouse; D019278:Matrix Metalloproteinase 3; D020780:Matrix Metalloproteinase 9