title: Induction of cartilage damage by overexpression of T cell interleukin-17A in experimental arthritis in mice deficient in interleukin-1.
abstract: OBJECTIVE
  To examine the capacity of T cell interleukin-17A (IL-17A; referred to hereinafter as IL-17) to induce cartilage damage during experimental arthritis in the absence of IL-1.
  
  
  METHODS
  Local IL-17 gene transfer was performed in the knee joint of IL-1-deficient mice and wild-type controls during streptococcal cell wall (SCW)-induced arthritis. Knee joints were isolated at various time points for histologic analysis of cartilage proteoglycan (PG) depletion. Expression of messenger RNA for inducible nitric oxide synthase, matrix metalloproteinases (MMPs) 3, 9, and 13, and ADAMTS-4 was determined by quantitative polymerase chain reaction analysis. VDIPEN staining was analyzed to study MMP-mediated cartilage damage. In addition, systemic anti-IL-1alpha/beta antibody treatment was performed in mice immunized with type II collagen and injected locally with an adenoviral vector expressing IL-17 or with control adenovirus. Knee joints were isolated and analyzed for cartilage PG depletion, chondrocyte death, and cartilage surface erosion.
  
  
  RESULTS
  During SCW-induced arthritis, local T cell IL-17 gene transfer turned this acute, macrophage-driven joint inflammation into a severe, chronic arthritis accompanied by aggravated cartilage damage. Of high interest, the IL-1 dependency of cartilage PG depletion was fully abrogated when IL-17 was locally overexpressed in the joint. Moreover, local IL-17 gene transfer increased MMP expression without the need for IL-1, although IL-1 remained essential for part of the cartilage VDIPEN expression. Furthermore, when IL-17 was overexpressed in the knee joints of mice with collagen-induced arthritis, anti-IL-1 treatment did not reduce the degree of chondrocyte death or cartilage surface erosion.
  
  
  CONCLUSIONS
  These data show the capacity of IL-17 to replace the catabolic function of IL-1 in cartilage damage during experimental arthritis.
authors.affiliation: University Medical Center St. Radboud, Nijmegen, The Netherlands. M.Koenders@reuma.umcn.nl <M.Koenders@reuma.umcn.nl>
authors.forename: Marije I
authors.initials: MI
authors.lastname: Koenders
authors.forename: Erik
authors.initials: E
authors.lastname: Lubberts
authors.forename: Birgitte
authors.initials: B
authors.lastname: Oppers-Walgreen
authors.forename: Liduine
authors.initials: L
authors.lastname: van den Bersselaar
authors.forename: Monique M
authors.initials: MM
authors.lastname: Helsen
authors.forename: Jay K
authors.initials: JK
authors.lastname: Kolls
authors.forename: Leo A B
authors.initials: LA
authors.lastname: Joosten
authors.forename: Wim B
authors.initials: WB
authors.lastname: van den Berg
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000276:immunology*; D002357:Cartilage Diseases / Q000276:immunology; D002358:Cartilage, Articular / Q000276:immunology; D007375:Interleukin-1 / Q000172:deficiency* / Q000276:immunology; D020381:Interleukin-17 / Q000096:biosynthesis / Q000276:immunology*; D007719:Knee Joint; D008297:Male; D051379:Mice; D023421:Models, Animal; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D007375:Interleukin-1; D020381:Interleukin-17