Potential role of Interleukin-32 for joint disease and elucidation of the downstream signaling

2014 Fiscal Year Final Research Report

• Project/Area Number: 24592280
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Orthopaedic surgery
• Research Institution: Keio University
• Principal Investigator: NIKI Yasuo 慶應義塾大学, 医学部, 講師 (10276298)
• Co-Investigator(Kenkyū-buntansha): NAKAYAMA Masanori 慶應義塾大学, 医学部, 助教 (70528249) ; TAKEDA Yuki 慶應義塾大学, 医学部, 助教 (20445307)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: インターロイキン32 / Toll様受容体 / 関節リウマチ / 変形性関節症

Outline of Final Research Achievements

IL-32 is known to induce various inflammatory cytokines and trigger the TLR signaling cascade, however, receptors and downstream signaling pathways remain to be clarified. We found that IL-32 upregulated PR3, in turn triggering PAR2 signaling. TNFα and typeⅠ interferon expression decreased with siRNA targeting TRIF. Initially IL-32-PAR2-TRIF pathway induce TNFα expression and latter pathway induces typeⅠ interferon expression via IRF. IL-32 signaling gradually increases typeⅠ interferon expression to translate innate to adaptive immunity and terminate acute inflammation . IL-32-PAR2-TRIF axis may have been gained during the evolution of mammalian immune systems in order to function not only as an extracellular sensor of bacterial and autologous proteases, but also as an interface between innate and adaptive immunity.

Free Research Field

膝関節、関節リウマチ