Analyses of novel NF-kB inhibitory signals

• Project/Area Number: 23591458
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: 膠原病・アレルギー・感染症内科学
• Research Institution: Chiba University
• Principal Investigator: SUZUKI KOTARO 千葉大学, 医学部附属病院, 講師 (90554634)
• Co-Investigator(Renkei-kenkyūsha): NAKAJIMA Hiroshi 千葉大学, 大学院医学研究院, 教授 (00322024)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2012: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2011: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: サイトカイン / BTLA / 肥満細胞 / NF-kB / IKK complex / IKK / mast cell / p53

Research Abstract

The regulatory mechanisms, which could be applicable for the treatment of allergic contact dermatitis, are still largely unknown. To determine roles of B and T lymphocyte attenuator (BTLA) in hapten-induced contact hypersensitivity (CHS), BTLA KO mice and wild-type (WT) mice were subjected to dinitrofluorobenzene (DNFB)-induced CHS. BTLA KO mice showed enhanced CHS as compared to WT mice. To evaluate the therapeutic potential of an agonistic agent for BTLA on CHS, the effects of an agonistic anti-BTLA antibody (6A6) on CHS were examined. In vivo injection of 6A6 suppressed CHS. Taken together, these results suggest that stimulation of BTLA with agonistic agents has therapeutic potential in CHS.

Research Products

• [Journal Article] Tumor suppressor p53 inhibits systemic autoimmune diseases by inducing regulatory T cells. (2013)
  • Author(s): Kawashima H, Takatori H, Suzuki K, Iwata A, Yokota M, Suto A, Minamino T, Hirose K, Nakajima H
  • Journal Title: J Immunol. Volume: 19 Issue: 7 Pages: 3614-3623
  • DOI: 10.4049/jimmunol.1300509
  • Peer Reviewed
• [Journal Article] Alteration of circulating miRNAs in SSc: miR-30b regulates the expression of PDGF receptor β. (2013)
  • Author(s): Tanaka S, Suto A, Ikeda K, Sanayama Y, Nakagomi D, Iwamoto T, Suzuki K, Kambe N, Matsue H, Matsumura R, Kashiwakuma D, Iwamoto I, Nakajima H.
  • Journal Title: Rheumatology Volume: 52 Issue: 11 Pages: 1963-1972
  • DOI: 10.1093/rheumatology/ket254
  • Peer Reviewed
• [Journal Article] Role of calcium ionophore A23187-induced activation of IkappaB kinase 2 in mast cells (2013)
  • Author(s): Hosokawa J, Suzuki K, Nakagomi D, Tamachi T, Takatori H, Suto A, Nakajima H
  • Journal Title: Int Arch Allergy Immunol Volume: 161 Issue: Suppl. 2 Pages: 37-43
  • DOI: 10.1159/000350357
  • Peer Reviewed
• [Journal Article] [18F]FDG uptake in proximal muscles assessed by PET/CT reflects both global and local muscular inflammation and provides useful information in the management of patients with polymyositis/dermatomyositis. (2013)
  • Author(s): Tanaka S et al
  • Journal Title: Rheumatology Volume: 52 Issue: 7 Pages: 1271-1278
  • DOI: 10.1093/rheumatology/ket112
  • Peer Reviewed
• [Journal Article] B and T lymphocyte attenuator inhibits LPS-induced endotoxic shock by suppressing Toll-like receptor 4 signaling in innate immune cells (2013)
  • Author(s): Kobayashi Y, Iwata A, Suzuki K, Suto A, Kawashima S, Saito Y, Owada T, Kobayashi M, Watanabe N, Nakajima H
  • Journal Title: Proc Natl Acad Sci U S A Volume: 110(13) Issue: 4 Pages: 890-8
  • DOI: 10.1002/art.37848
  • Peer Reviewed
• [Journal Article] Therapeutic potential of B and T lymphocyte attenuator expressed on CD8+ T cells for contact hypersensitivity. (2013)
  • Author(s): Nakagomi D, Suzuki K, Hosokawa J, Kobayashi Y, Suto A, Takatori H, Watanabe N, Matsue H, Murphy TL, Murphy KM, Shimada S, Nakajima H.
  • Journal Title: J Invest Dermatol. Volume: 133 Issue: 3 Pages: 702-702
  • DOI: 10.1038/jid.2012.396
  • Peer Reviewed
• [Journal Article] Roles of mast cells in the pathogenesis of inflammatory myopathy. (2013)
  • Author(s): Yokota M, Suzuki K, Tokoyoda K, Meguro K, Hosokawa J, Tanaka S, Ikeda K, Mikata T, nakayama T, Kohsaka H, Nakajima H.
  • Journal Title: Arthritis Res Ther Volume: 16(2)
  • Peer Reviewed
• [Journal Article] Subtilase cytotoxin enhances Escherichia coli survival in macrophages by suppression of nitric oxide production through the inhibition of NF-κB activation (2012)
  • Author(s): Tsutsuki H, Yahiro K, Suzuki K, Suto A, Ogura K, Nagasawa S, Ihara H, Shimizu T, Nakajima H, Moss J, Noda M
  • Journal Title: Infect Immun Volume: 80 Issue: 11 Pages: 3939-51
  • DOI: 10.1128/iai.00581-12
  • Peer Reviewed
• [Journal Article] Critical roles of IĸB kinase subunits in mast cell degranulation. (2012)
  • Author(s): Nakagomi D, Suzuki K, Nakajima H.
  • Journal Title: Int Arch Allergy Immunol. Volume: 158 Suppl 1 Issue: Suppl. 1 Pages: 92-95
  • DOI: 10.1159/000337800
  • Peer Reviewed
• [Journal Article] STAT4 is required for IFN-β-induced MCP-1 mRNA expression in murine mast cells (2011)
  • Author(s): Iida K, Suzuki K, Yokota M, Nakagomi D, Wakashin H, Iwata A, Kawashima H, Takatori H, Nakajima H
  • Journal Title: Int. Arch. Allergy Immunol Volume: 155 Issue: Suppl. 1 Pages: 71-6
  • DOI: 10.1159/000327300
  • Peer Reviewed
• [Journal Article] Tumor suppressor p53 functions as a negative regulator in IgE-mediated mast cell activation (2011)
  • Author(s): Suzuki K, Murphy SH, Xia Y, Yokota M, Nakagomi D, Liu F, Verma IM, Nakajima H
  • Journal Title: PLoS One Volume: 6 Issue: 9 Pages: e25412-e25412
  • DOI: 10.1371/journal.pone.0025412
  • Peer Reviewed
• [Presentation] Tumor suppressos p53 inhibits systemic autoimmune diseases by inducing regulatory T cells (2013)
  • Author(s): 川島広稔、高取宏昌、鈴木浩太郎、岩田有史、横田雅也、須藤明、南野徹、廣瀬晃一、中島裕史
  • Organizer: 第42回日本免疫学会学術集会
  • Place of Presentation: 幕張、千葉
  • Year and Date: 2013-12-13
• [Presentation] SOCS3 expressed in macrophages inhibits contact hypersensitivity by suppressing MMP-12 production (2013)
  • Author(s): 中込大樹、鈴木浩太郎、中島裕史
  • Organizer: 第42回日本免疫学会学術集会
  • Place of Presentation: 幕張、千葉
  • Year and Date: 2013-12-13
• [Presentation] 接触過敏症におけるマスト細胞産生性IFN-gの役割 (2013)
  • Author(s): 中込大樹、鈴木浩太郎、中島裕史
  • Organizer: 第63回日本アレルギー学会秋期学術大会
  • Place of Presentation: 四谷、東京
  • Year and Date: 2013-11-29
• [Presentation] 中枢神経ループス患者における脳脊髄液中BAFF値の検討 (2012)
  • Author(s): 細川淳一、鈴木浩太郎、中込大樹、岩本太郎、池田啓、中島裕史
  • Organizer: 第56回日本リウマチ学会総会・学術集会
  • Place of Presentation: 品川、東京
  • Year and Date: 2012-04-27
• [Presentation] 肥満細胞内Ca-IKK2シグナルの役割 (2011)
  • Author(s): 鈴木浩太郎
  • Organizer: 第４０回日本免疫学会総会・学術集会
  • Place of Presentation: 千葉市
• [Presentation] Tumor suppressor p53 inhibits systemic autoimmune diseases by inducing regulatory T cells.
  • Author(s): Hirotoshi Kawashima, Hiroaki Takatori, Kotaro Suzuki, Masaya Yokota, Akira Suto, Koichi Hirose, Hiroshi Nakajima.
  • Organizer: 日本免疫学会
  • Place of Presentation: 千葉（幕張メッセ）
• [Presentation] SOCS3 expressed in macrophages inhibits contct hypersensitivity by suppressing MMP-12 production.
  • Author(s): Daiki Nakagomi, Kotaro Suzuki, kazuyuki Meguro, Junichi Hosokawa, Tomohiro Tamachi, Hiroaki Takatori, Akira Suto, Hiroshi Nakajima.
  • Organizer: 日本免疫学会
  • Place of Presentation: 千葉（幕張メッセ）
• [Presentation] Role of IKK complex-independent IkBa phosphorylation in mast cells.
  • Author(s): Junichi Hosokawa, Kotaro Suzuki, Hiroshi Nakajima.
  • Organizer: 日本免疫学会
  • Place of Presentation: 神戸（ 神戸国際会議場）
• [Presentation] B and T lymphocyte attenuator expressed on CD8+ T cells suppresses contact hypersensitivity reaction.
  • Author(s): Daiki Nakagomi, Kotaro Suzuki, Hiroshi Nakajima.
  • Organizer: 日本免疫学会
  • Place of Presentation: 神戸（ 神戸国際会議場）
• [Remarks]
  • URL: http://www.m.chiba-u.jp/class/allergy/