Novel activation pathway of NF-kB via LUBAC in patient with rheumatoid arthritis

• Project/Area Number: 22591685
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Orthopaedic surgery
• Research Institution: Osaka University
• Principal Investigator: TOMITA Tetsuya 大阪大学, 医学系研究科, 寄附講座准教授 (30283766)
• Co-Investigator(Kenkyū-buntansha): YOSHIKAWA Hideki 大阪大学, 大学院・・医学系研究科, 教授 (60191558) ; IWAI Kazuhiro 大阪大学, 大学院・医学系研究科, 教授 (60252459) ; KUNUGIZA Yasuo 大阪大学, 大学院・医学系研究科, 助教 (60507193)
• Project Period (FY): 2010 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2012: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2011: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2010: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: arthritis / inflammation / NF kappa B / LUBAC / 関節リウマチ / NF-kB

Research Abstract

In this study, we investigated the expression of LUBAC in patients with rheumatoid arthritis. OA samples were used as control in this study. Both in RA and OA synovium, the expression of LUBAC（HOIP／HOIL-1L）was confirmed using immuno-histochemistry. The expression in RA was up-regulated compared to OA. Furthermore, the expression of LUBAC（HOIP／HOIL-1L）was confirmed in the serum of both RA and OA patients. The expression in RA was significantly higher compared to OA. The results in this study suggested that the expression of HOIP／HOIL-1L may play an important role in the activation pathway of NF-kB in patients with rheumatoid arthritis.

Research Products

• [Journal Article] TNF inhibitors induce discoid fibrosis in the sublining layers of the synovium with degeneration of synoviocytes in rheumatoid arthritis (2013)
  • Author(s): Hirohata S
  • Journal Title: Rheumatol Int Volume: 11 Issue: 10 Pages: 2473-2481
  • DOI: 10.1007/s00296-013-2743-y
  • Peer Reviewed
• [Journal Article] A pro-inflammatory role for A20 and ABIN family proteins in human fibroblast-like synoviocytes in rheumatoid arthritis (2012)
  • Author(s): Igarashi, H., Yahagi, Y., Saika, T., Hashimoto, J., Tomita, T., Yoshikawa.H., Ishihara, K.
  • Journal Title: Immunol Lett Volume: 30 Pages: 246-53
  • Peer Reviewed
• [Journal Article] A pro-inflammatoty role for A20 and ABIN family proteins in human fibroblast-like synoviocytes in rheumatoid arthritis (2011)
  • Author(s): Igarashi H, Ishihara K, et al
  • Journal Title: Immunol.Lett. Volume: 141 Issue: 2 Pages: 246-253
  • DOI: 10.1016/j.imlet.2011.10.011
  • Peer Reviewed
• [Journal Article] Staphylococcal scalded skin syndrome after intra-articular injection of hyaluronic acid (2011)
  • Author(s): Kunugiza Y, Tani M, Tomita T, Yoshikawa H
  • Journal Title: Mod Rheumatol Volume: 21 Pages: 316-9
  • NAID: 10029362398
  • Peer Reviewed
• [Journal Article] Tocilizumab, a humanized anti-interluekin-6 receptor antibody, ameriolated clinical symptoms and MRI findings of a patient with ankylosing spondylitis (2011)
  • Author(s): Shima Y, Tomita T, IshiiT, Morishima A, Maeda Y, Ogata A, Kishimoto T, Tanaka T
  • Journal Title: Mod Rheumatol Volume: 21 Pages: 436-9
  • Peer Reviewed
• [Journal Article] Recurrent allergic bronchopulmonary aspergillosis in a natient with rheumatoid arthritis treated with etanercent and tocilizumab (2011)
  • Author(s): Honda H, Kida H, Yoshida M, Tomita T, Fujii M, Ihara S, Goya S, Tachibana I, Kawase I
  • Journal Title: Mod Rheumatol Volume: 21 Pages: 660-4
  • Peer Reviewed
• [Journal Article] Indcution of type B synoviocyte-like cells from plasmacytoid dendritic cells of the bone marrow in rheumatoid arthritis and osteoarthritis (2011)
  • Author(s): Hirohata S, Nagai T, Asako K, Tomita T, Yoshikawa H
  • Journal Title: Clin Immunol Volume: 140 Pages: 276-83
  • Peer Reviewed
• [Journal Article] Enhanced expression of mRNA for FK506-binding protein 5 in bone marrow CD34+ positive cells patients with rheumatoid arthritis. (2010)
  • Author(s): Matsushita R, Tomita T, Yoshikawa H
  • Journal Title: Clin Exp Rheumatol Volume: 28 Pages: 87-90
  • Peer Reviewed
• [Journal Article] A hydrocellular foam dressing versus gauze : effects on the healing of rat excisional wounds. (2010)
  • Author(s): Kunugiza Y, Tomita T, Yoshikawa H
  • Journal Title: J Wound Care Volume: 19 Pages: 10-14
  • Peer Reviewed
• [Journal Article] Inorganic polyphosphate differentiates human mesenchymal stem cells into osteoblastic cells. (2010)
  • Author(s): Morimoto D, Tomita T, Yoshikawa H
  • Journal Title: J Bone Miner Metab Volume: 28 Pages: 418-423
  • NAID: 10027208196
  • Peer Reviewed
• [Journal Article] TP53 mutations coincide with the ectopic expression of activation-induced cytidine deaminase in the fibroblast-like synoviocytes derived from a fraction of patients with rheumatoid arthritis. (2010)
  • Author(s): Igarashi H, Tomita T, Yoshikawa H
  • Journal Title: Clin Exp Immunol. Volume: 161
  • Peer Reviewed
• [Presentation] A novel peptide inhibiting the binding between C1q and immunoglobulin ameliorates joint destruction in rats with collagen-induced arthritis (2013)
  • Author(s): Moriguchi Y, Zhang DW, Shiba T, Kunugiza Y , Yoshikawa H , Asamori C, Tomita T
  • Organizer: Spotlight session
  • Place of Presentation: サンアントニオ(米国)、米国整形外科研究学会(ORS)、
  • Year and Date: 2013-01-25
• [Presentation] A novel peptide inhibiting the binding between C1q and immunoglobulin ameliorates joint destruction in rats with collagen-induced arthritis (2012)
  • Author(s): Moriguchi Y, Zhang DW, Shiba T, Kunugiza Y , Yoshikawa H , Tomita T
  • Place of Presentation: ワシントンDC(米国)、米国リウマチ学会(ACR)
  • Year and Date: 2012-11-12
• [Presentation] コラーゲン誘導関節炎ラットにおけるC1q-IgG 結合阻害ペプチドの治療効果 (2012)
  • Author(s): 冨田哲也、 森口悠、 Zhang DW、 椚座康夫、朝森千永子、吉川秀樹
  • Organizer: 第33回日本炎症・再生医学会
  • Place of Presentation: 福岡
  • Year and Date: 2012-07-05
• [Presentation] A novel peptide inhibiting binding between C1q and immunocomplex suppresses joint destruction in experimental arthritis (2012)
  • Author(s): Tetsuya Tomita
  • Organizer: 4^<th> Annual Asia Tides
  • Place of Presentation: Tokyo
  • Year and Date: 2012-02-29
• [Presentation] 関節リウマチにおける NFκB 活性化経路の新規ユビキチンリガーゼ LUBAC の発現 (2011)
  • Author(s): 冨田哲也、 森口悠、 椚座康夫、徳永文稔、岩井一宏、吉川秀樹
  • Organizer: 第32回日本炎症・再生医学会
  • Place of Presentation: 京都
  • Year and Date: 2011-06-03
• [Presentation] Parthenolide, a natural inhibitor of nuclear factor-kappa B, inhibits human chondrocytes degradation in vitro and improved symptoms of patients with osteoarthritis in vivo (2010)
  • Author(s): Tomita T, Kunugiza Y, Yoshikawa H
  • Organizer: Annual European Congress of Rheumatology 2010
  • Place of Presentation: Rome, Italy
  • Year and Date: 2010-06-18
• [Presentation] Parthenolide, a natural inhibitor of NFkB, inhibits chondrocytes degradation and improved symptoms of OA patients. (2010)
  • Author(s): Tomita T, Kunugiza Y, Yoshikawa H
  • Organizer: 第10回日本抗加齢医学会総会
  • Place of Presentation: 京都
  • Year and Date: 2010-06-12
• [Presentation] A novel peptide inhibiting the binding between C1q and immunoglobulin ameliorates joint destruction in rats with collagen-induced arthritis
  • Author(s): Moriguchi Y
  • Organizer: 米国整形外科研究学会
  • Place of Presentation: サンアントニオ（米国）
• [Presentation] A novel peptide inhibiting the binding between C1q and immunoglobulin ameliorates joint destruction in rats with collagen-induced arthritis.
  • Author(s): Moriguchi Y
  • Organizer: 米国リウマチ学会
  • Place of Presentation: ワシントンDC（米国）
• [Presentation] コラーゲン誘導関節炎ラットにおけるC1q-IgG結合阻害ペプチドの治療効果
  • Author(s): 冨田 哲也
  • Organizer: 第33回日本炎症・再生医学会
  • Place of Presentation: 福岡