title: Dual role of interleukin-17 in pannus growth and osteoclastogenesis in rheumatoid arthritis.
abstract: BACKGROUND
  In a murine model, interleukin (IL)-17 plays a critical role in the pathogenesis of arthritis. There are controversies, however, regarding whether IL-17 is a proinflammatory mediator in rheumatoid arthritis (RA). We previously established an ex vivo cellular model using synovial tissue (ST)-derived inflammatory cells, which reproduced pannus-like tissue growth and osteoclastic activity in vitro. Using this model, we investigated the effects of IL-17 on pannus growth and osteoclastogenesis in RA.
  
  
  METHODS
  Inflammatory cells that infiltrated synovial tissue from patients with RA were collected without enzyme digestion and designated as ST-derived inflammatory cells. ST-derived inflammatory cells were cultured in the presence or absence of IL-17 or indomethacin, and the morphologic changes were observed for 4 weeks. Cytokines produced in the culture supernatants were measured by using enzyme-linked immunosorbent assay kits. Osteoclastic activity was assessed by the development of resorption pits in calcium phosphate-coated slides.
  
  
  RESULTS
  Exogenous addition of IL-17 dramatically enhanced the spontaneous production of IL-6 and prostaglandin E₂ (PGE₂) by the ST-derived inflammatory cells, while it had no effect on the production of tumor necrosis factor (TNF)-α and macrophage colony-stimulating factor (M-CSF). Furthermore, IL-17 did not affect the spontaneous development of pannus-like tissue growth and osteoclastic activity by the ST-derived inflammatory cells. On the other hand, IL-17 enhanced pannus-like tissue growth, the production of TNF-α and M-CSF and the development of osteoclastic activity in the presence of indomethacin, an inhibitor of endogenous prostanoid production, while exogenous addition of PGE₁ suppressed their activities.
  
  
  CONCLUSIONS
  The present study suggests that IL-17 induces negative feedback regulation through the induction of PGE₂, while it stimulates proinflammatory pathways such as inflammatory cytokine production, pannus growth and osteoclastogenesis in RA.
authors.affiliation: Division of Rheumatology and Allergology, Department of Internal Medicine, St, Marianna University School of Medicine, 2-16-1 Sugao, Miyamae-ku, Kawasaki 216-8511, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ito
authors.forename: Hidehiro
authors.initials: H
authors.lastname: Yamada
authors.forename: Toshiko N
authors.initials: TN
authors.lastname: Shibata
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Mitomi
authors.forename: So
authors.initials: S
authors.lastname: Nomoto
authors.forename: Shoichi
authors.initials: S
authors.lastname: Ozaki
mesh_terms: D001172:Arthritis, Rheumatoid / Q000276:immunology / Q000378:metabolism*; D001862:Bone Resorption / Q000276:immunology / Q000378:metabolism*; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D025461:Feedback, Physiological / Q000502:physiology; D006097:Granulation Tissue / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D020381:Interleukin-17 / Q000276:immunology / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D020381:Interleukin-17