Prokineticin-receptor systems in patients with rheumatoid arthritis

2021 Fiscal Year Final Research Report

• Project/Area Number: 17K16214
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Collagenous pathology/Allergology
• Research Institution: Jikei University School of Medicine
• Principal Investigator: Noda Kentaro 東京慈恵会医科大学, 医学部, 助教 (30547914)
• Project Period (FY): 2021-03-01 – 2022-03-31
• Keywords: prokineticin2 / prokineticin receptor / 関節リウマチ

Outline of Final Research Achievements

In this study, we collected synovial tissue, plasma, synovial fluid, and synovial fibroblasts (SF) from RA and OA patients to analyze the function of PK2 using immunohistochemistry, enzyme-linked immunosorbent assays, and tissue superfusion studies. PK2 and its receptors prokineticin receptor (PKR) 1 and 2 were expressed in RA and OA synovial tissues. PKR1 expression was downregulated in RA synovial tissue compared with OA synovial tissue. The PK2 concentration was higher in RA synovial fluid than in OA synovial fluid but similar between RA and OA plasma. PK2 suppressed the production of IL-6 from TNFα-prestimulated OA-SF, and this effect was attenuated in TNFα-prestimulated RA-SF. This phenomenon was accompanied by the upregulation of PKR1 in OA-SF. This study provides a new model to explain some aspects underlying the chronicity of inflammation in RA.

Free Research Field

リウマチ・膠原病学

Academic Significance and Societal Importance of the Research Achievements

関節リウマチ患者の関節滑膜においてPK2-PKR1系による炎症抑制効果がPKR1の発現低下により減少するため、関節炎の慢性炎症を継続させる可能性が考えられた。関節局所のPKR1の発現を高めることが関節における局所の炎症をコントロールするための戦略となり得る可能性が示唆された。