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Open Access Open Badges Research article

Dual role of interleukin-17 in pannus growth and osteoclastogenesis in rheumatoid arthritis

Hiroshi Ito1, Hidehiro Yamada1*, Toshiko N Shibata1, Hirofumi Mitomi1, So Nomoto2 and Shoichi Ozaki1

Author Affiliations

1 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

2 Department of Orthopaedic Surgery and Rheumatology, Saiseikai Yokohamashi Tobu Hospital, 3-6-1, Shimosueyoshi, Tsurumi-ku, Yokohama 230-8765, Japan

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Arthritis Research & Therapy 2011, 13:R14  doi:10.1186/ar3238

Published: 4 February 2011



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.


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.


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.


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.