Analysis of disease development in psoriatic arthritis using psoriatic model mouse

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K10162
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Dermatology
• Research Institution: Kochi University
• Principal Investigator: NAKAJIMA HIDEKI 高知大学, 教育研究部医療学系臨床医学部門, 講師 (70314995)
• Co-Investigator(Kenkyū-buntansha): 中島 喜美子 高知大学, 教育研究部医療学系臨床医学部門, 准教授 (20403892) ; 佐野 栄紀 高知大学, 教育研究部医療学系臨床医学部門, 教授 (80273621)
• Research Collaborator: NAKAJIMA KIMIKO , 教育研究部医療学系臨床医学部門, 准教授 (20403892)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 乾癬モデルマウス / K5.Stat3 / DNFB / 付着部炎 / 乾癬性関節炎 / TNF-α / LRG

Outline of Final Research Achievements

Repetitive DNFB painting on hind paws of K5. Stat3C mice resulted in prominent joint swelling. Alternatively, LRG deletion induced a significant decrease in joint swelling and foot pad thickness in K5. Stat3C mice after chronic CHS. Histological finding revealed that chronic CHS caused subcutaneous and peri-tendinous infiltration of inflammatory cells at day 7, and then provoked enthesitis involving periarticular muscle at day 14. Chronic CHS induced an upregulation of LRG, IL-1β, TGF-β, IL-6, IL-12p35, IL-17A and IL-17F in articular and periarticular tissues of K5. Stat3C mice paws at day 7. In contrast, K5.Stat3C: LRG－/－ mice displayed downregulation of TNF-α and IL-17A compared with K5.Stat3C: LRG+/+ mice. Collectively, these results show that chornic DNFB application on paws of K5.Stat3C mice can induce enthesitis through upregulation of LRG, inflammatory cytokines and IL-17 in K5.Stat3C mice.

Free Research Field

乾癬

Academic Significance and Societal Importance of the Research Achievements

乾癬性関節炎の発症機序は現在まで明らかではないが、今回の乾癬モデルマウスを使った実験により関節表面の皮膚病変が、関節腫脹や付着部炎を誘導することを証明した。乾癬病変におけるサイトカインの増加が、腱を通じて関節腔および腱付着部まで影響を及ぼし炎症の悪化と腱の肥厚を誘導することが明らかになった。