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

作者：Ito Hiroshi; Yamada Hidehiro^*; Shibata Toshiko N; Mitomi Hirofumi; Nomoto So; Ozaki Shoichi

来源：Arthritis Research and Therapy, 2011, 13(1): R14.

DOI：10.1186/ar3238

Introduction: 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 E(2) (PGE(2)) by the ST-derived inflammatory cells, while it had no effect on the production of tumor necrosis factor (TNF)-alpha 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-alpha and M-CSF and the development of osteoclastic activity in the presence of indomethacin, an inhibitor of endogenous prostanoid production, while exogenous addition of PGE(1) suppressed their activities.
Conclusions: The present study suggests that IL-17 induces negative feedback regulation through the induction of PGE(2), while it stimulates proinflammatory pathways such as inflammatory cytokine production, pannus growth and osteoclastogenesis in RA.

• 出版日期2011