Identification of functional regions the soluble ST2 protein against inflammation, and its possible application for novel drugs.

• Project/Area Number: 19590318
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Pathological medical chemistry
• Research Institution: Jichi Medical University
• Principal Investigator: TOMINAGA Shinichi Jichi Medical University, 医学部, 教授 (70155571)
• Co-Investigator(Kenkyū-buntansha): YANAGISAWA Ken 自治医科大学, 医学部, 教授 (50182366) ; OHTA Satoshi 自治医科大学, 医学部, 助教 (40528428) ; TAKEZAKO Naoki 独立行政法人国立病院機構災害医療センター, 診療部, 医長 (80424026)
• Project Period (FY): 2007 – 2009
• Project Status: Completed (Fiscal Year 2009)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2009: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2008: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2007: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: ST2遺伝子 / 糖鎖修飾 / 抗炎症作用 / アレルギー・ぜんそく / シグナル伝達 / タンパク質 / 糖鎖 / 免疫学

Research Abstract

ST2 protein is induced in the case of allergic diseases, such as bronchial asthma, in parallel with disease activity. Possible usage of the functional region of the ST2 protein as a novel drug against inflammatory reaction in allergic diseases, we clarified that core protein itself is able to suppress inflammation, and its glycosylation enhanced the inhibitory activity. We are now identifying minimum effective region of the ST2 protein.

Research Products

• [Journal Article] ST2 gene expression is proliferation-dependent and its ligand, IL-33, induces inflammatory reaction in endothelial cells (2010)
  • Author(s): Aoki, S., Hayakawa, M., Ozaki, H., Takezako, N., Obata, H., Ibaraki, N., Tsuru, T., Tominaga, S., Yanagisawa, K.
  • Journal Title: Mol. Cell. Biochem. 335 Pages: 75-81
  • Peer Reviewed
• [Journal Article] Increased levels of interleukin-33 in sera and synovial fluids from patients with active rheumatoid arthritis (2010)
  • Author(s): Matsuyama, Y., Okazaki, H., Tamemoto, H., Kimura, H., Kamata, Y., Nagatani, K., Nagashima, T., Hayakawa, M., Iwamoto, M., Yoshio, T., Tominaga, S., Minota, S.
  • Journal Title: J. Rheumatol. 37 Pages: 18-25
  • Peer Reviewed
• [Journal Article] ST2 gene expression is proliferation-dependent and its ligand, IL-33, induces inflammatory reaction in endothelial cells (2010)
  • Author(s): Shinsuke Aoki, et al.
  • Journal Title: Mol.Cell.Biochem. VOL.335 Pages: 75-81
  • Peer Reviewed
• [Journal Article] Mature interleukin-33 is produced by calpain-mediated cleavage in vivo (2009)
  • Author(s): Hayakawa, M., Hayakawa, H., Matsuyama, Y., Tamemoto, H., Okazaki, H., Tominaga, S.
  • Journal Title: Biochem. Biophys. Res. Commun. 387 Pages: 218-222
  • Peer Reviewed
• [Journal Article] IL-1R-related protein ST2 suppressed the initial stage of bleomycin-induced lung injury (2009)
  • Author(s): Mato, N., Fujii, M., Hakamata, Y., Kobayashi, E., Sato, A., Hayakawa, M., Ohto-Ozaki, H., Bando, M., Ohno, S., Tominaga, S., Sugiyama, Y.
  • Journal Title: Eur. Respir. J. 33 Pages: 1415-1428
  • Peer Reviewed
• [Journal Article] IL-1R-related protein ST2 suppressed the initial stage of bleomycin-induced lung injury (2009)
  • Author(s): Naoko Mato, et al.
  • Journal Title: Eur.Respir.J. VOL.33 Pages: 1415-1428
  • Peer Reviewed
• [Journal Article] Mature interleukin-33 is produced by calpain-mediated cleavage in vivo (2009)
  • Author(s): Morisada Hayakawa, et al.
  • Journal Title: Biochem.Biophys.Res.Commun. VOL.387 Pages: 218-222
  • Peer Reviewed
• [Journal Article] TRAF6 is a critical signal transducer in IL-33 signaling pathway. (2008)
  • Author(s): Funakoshi-Tago, M., Tago, K., Hayakawa, M., Tominaga, S., Ohshio, T., Sonoda, Y., Kasahara, T.
  • Journal Title: Cell. Signal. 20 Pages: 1679-1686
  • Peer Reviewed
• [Journal Article] インターロイキン-33 (2008)
  • Author(s): 早川 盛禎, 他
  • Journal Title: 分子細胞治療(Cellular Molecular Medicine) 7 Pages: 68-68
• [Journal Article] TRAF6 is a critical signal transducer in IL-33 signaling pathway (2008)
  • Author(s): Megumi Funakoshi-Tago, et al.
  • Journal Title: Cellular Signalling 20 Pages: 1679-1686
  • Peer Reviewed
• [Journal Article] Soluble ST2 blocks IL-33 signaling in allergic airway inflammation (2007)
  • Author(s): Hayakawa, H., Hayakawa, M., Kume, A., Tominaga, S.
  • Journal Title: J. Biol. Chem. 282 Pages: 26369-26380
  • Peer Reviewed
• [Journal Article] ST2 gene induced by type 2 helper T cell (Th2) and proinflammatory cytokine stimuli may modulate lung injury and fibrosis (2007)
  • Author(s): Tajima, S., Bando, M., Ohno, S., Sugiyama, Y., Oshikawa, K., Tominaga, S., Itoh, K., Takada, T., Suzuki, E., Gejyo, F.
  • Journal Title: Exp. Lung Res. 33 Pages: 81-97
  • Peer Reviewed
• [Journal Article] ST2 gene induced by type 2 helper T cell (Th2)and proinflammatory cytokine stimuli may modulate lung injury and fibrosis (2007)
  • Author(s): Shunji Tajima, et. al.
  • Journal Title: Experimental Lung Research 33 Pages: 81-97
• [Journal Article] Soluble ST2 blocks IL-33 signaling in allergic airway inflammation (2007)
  • Author(s): Hiroko Hayakawa, et. al.
  • Journal Title: The Journal of Biological Chemistry 282 Pages: 26369-26380
• [Presentation] IL-33 induces inflammatory reaction in endothelial cells, and its receptor, ST2L is expressed in growth-dependent manner. (IL-33は内皮細胞に炎症反応を惹起し, その受容体のST2Lは増殖依存性に内皮細胞に発現する. ) (2009)
  • Author(s): 柳澤健, 太田聡, 松儀実広, 富永眞一
  • Organizer: 第32回日本分子生物学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2009-12-12
• [Presentation] IL-33は内皮細胞に炎症反応を惹起し、その受容体のST2Lは増殖依存性に内皮細胞に発現する (2009)
  • Author(s): 柳澤健, 他
  • Organizer: 第32回日本分子生物学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2009-12-12
• [Presentation] The immunological reactions induced by intraperitoneal administration of IL-33 were attenuated in ST2 transgenic mice. (ST2トランスジェニックマウスを用いた, ST2の抗IL-33効果の検討.) (2009)
  • Author(s): 尾崎裕美, 黒岩憲二, 早川盛禎, 為本浩至, 富永眞一
  • Organizer: 第32回日本分子生物学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2009-12-11
• [Presentation] ST2トランスジェニックマウスを用いた、ST2の抗IL-33効果の検討 (2009)
  • Author(s): 尾崎裕美, 他
  • Organizer: 第32回日本分子生物学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2009-12-11
• [Presentation] Increased levels of interleukin-33 in sera and synovial fluids from patients with active rheumatoid arthritis (2009)
  • Author(s): 松山泰, 岡崎仁昭, 為本浩至, 早川盛禎, 岩本雅弘, 富永眞一, 簑田清次
  • Organizer: 第32回日本分子生物学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2009-12-10
• [Presentation] ST2遺伝子と病気 (2008)
  • Author(s): 富永眞一, 早川裕子, 早川盛禎, 柳澤健
  • Organizer: 3学会合同大会2008自然免疫の最前線第73回日本インターフェロン・サイトカイン学会学術集会/第19回日本生体防御学会学術集会/第45回補体シンポジウム3学会合同集会
  • Place of Presentation: 札幌
  • Year and Date: 2008-07-11
• [Presentation] ST2遺伝子と病気 (2008)
  • Author(s): 富永 眞一, 他
  • Organizer: 第73回インターフェロン・サイトカイン学会学術集会, 第19回日本生体防御学会学術集会, 第45回補体シンポジウム3学会合同集会
  • Place of Presentation: 札幌
  • Year and Date: 2008-07-11
• [Presentation] 分泌型ST2タンパク質による単球系細胞の樹状細胞への分化抑制作用について (2007)
  • Author(s): 竹迫直樹, 早川裕子, 早川盛禎, 松儀実広, 柳澤健, 村尾捷利, 富永眞一
  • Organizer: 第30回日本分子生物学会年会・第80回日本生化学会大会合同年会
  • Place of Presentation: 横浜
  • Year and Date: 2007-12-14
• [Presentation] 分泌型ST2によるIL-33シグナル伝達系の抑制 (2007)
  • Author(s): 早川裕子, 早川盛禎, 久米晃啓, 富永眞一
  • Organizer: 第30回日本分子生物学会年会・第80回日本生化学会大会合同年会
  • Place of Presentation: 横浜
  • Year and Date: 2007-12-14
• [Presentation] 分泌型ST2によるIL-33シグナル伝達系の抑制 (2007)
  • Author(s): 早川 裕子, 他
  • Organizer: 第30回日本分子生物学会年会・第80回日本生化学会大会合同大会
  • Place of Presentation: 横浜
  • Year and Date: 2007-12-14
• [Presentation] 分泌型ST2タンパク質による単球系細胞の樹状細胞への分化抑制作用について (2007)
  • Author(s): 竹迫 直樹, 他
  • Organizer: 第30回日本分子生物学会年会・第80回日本生化学会大会合同大会
  • Place of Presentation: 横浜
  • Year and Date: 2007-12-14
• [Presentation] Dynamic subcellular localization of atypical small GTPase kappaB-Ras and its possible contribution to oncogenic signals (2007)
  • Author(s): 多胡憲治, 多胡めぐみ, 水野憲一, 笠原忠, 富永眞一, 伊東広
  • Organizer: 第30回日本分子生物学会年会・第80回日本生化学会大会合同年会
  • Place of Presentation: 横浜
  • Year and Date: 2007-12-13
• [Presentation] Dynamic subcellular localization of atypical small GTPase kappaB-Ras and its possible contribution to oncogenic signals (2007)
  • Author(s): 多胡 憲治, 他
  • Organizer: 第30回日本分子生物学会年会・第80回日本生化学会大会合同大会
  • Place of Presentation: 横浜
  • Year and Date: 2007-12-13
• [Presentation] IL-33シグナル伝達経路におけるTRAF6の役割の解析 (2007)
  • Author(s): 多胡めぐみ, 多胡憲治, 早川盛禎, 富永眞一, 園田よし子, 笠原忠
  • Organizer: 第30回日本分子生物学会年会・第80回日本生化学会大会合同年会
  • Place of Presentation: 横浜
  • Year and Date: 2007-12-12
• [Presentation] IL-33シグナル伝達経路におけるTRAF6の役割の解析 (2007)
  • Author(s): 多胡 めぐみ, 他
  • Organizer: 第30回日本分子生物学会年会・第80回日本生化学会大会合同大会
  • Place of Presentation: 横浜
  • Year and Date: 2007-12-12
• [Presentation] Soluble ST2 suppresses ST2L-based IL-33 signaling pathway (2007)
  • Author(s): Hayakawa, M., Hayakawa, H., Kume, A., Kuroiwa, K., Hakamata, Y., Tominaga, S.
  • Organizer: 15th Annual Meeting of the International Cytokine Society, Cytokines in Health and Disease
  • Place of Presentation: San Francisco, California
  • Year and Date: 2007-10-27
• [Presentation] Soluble ST2 suppresses ST2L-based IL-33 signaling pathway (2007)
  • Author(s): Morisada Hayakawa, et. al.
  • Organizer: 15^<th> Annual Meeting of the International Cytokine Society, Cytokines in Health and Disease
  • Place of Presentation: San Francisco,California
  • Year and Date: 2007-10-27
• [Presentation] ST2 works to suppress bleomycin induced lung injury (2007)
  • Author(s): Mato, N., Bando, M., Ohno, S., Tominaga, S., Sugiyama, Y.
  • Organizer: 2007 ATS International Conference in San Francisco
  • Place of Presentation: San Francisco, California
  • Year and Date: 2007-05-21
• [Presentation] ST2 works to suppress bleomycin induced lung injury (2007)
  • Author(s): Naoko Mato, et. al.
  • Organizer: 2007 ATS International Conference in San Francisco
  • Place of Presentation: San Francisco,California
  • Year and Date: 2007-05-21
• [Presentation] Incadronate can induce apoptosis in monocytic cells (2007)
  • Author(s): Miwa, A., Takezako, N., Hayakawa, M., Yanagisawa, K., Tominaga, S.
  • Organizer: XIth International Myeloma Workshop and the IVth International Workshop on Waldenstrom's Macroglobulinemia
  • Place of Presentation: Kos Island, Greece