Regulation of macrophage in adipose tissue by CXCL14 and its receptor.

• Project/Area Number: 25860304
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Experimental pathology
• Research Institution: Tokyo Metropolitan Institute of Medical Science
• Principal Investigator: TANEGASHIMA Kosuke 公益財団法人東京都医学総合研究所, 生体分子先端研究分野, 主任研究員 (20507678)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: CXCL14 / 炎症 / 炎症反応 / CXCL12 / CXCR4

Outline of Final Research Achievements

Disruption of CXCL14 in mice ameliorates obesity-induced chronic inflammation. We aimed to investigate how CXCL14 activates inflammatory signaling at the molecular level. We found that CXCL14 specifically bound to a TLR9-ligand, CpG DNA and acted as a cofactor. CXCL14/CpG DNA complex was efficiently incorporated into dendritic cells and macrophages and induced robust expression of Th1 type inflammatory cytokines. These results suggested that CXCL14 plays a new role for the activation of the innate immune pathway.

Research Products

• [Journal Article] Efficient one-pot synthesis of CXCL14 and its derivative using an N-sulfanylethylanilide peptide as a peptide thioester equivalent and their biological evaluation (2015)
  • Author(s): Kohei Tsuji, Kosuke Tanegashima, Kohei Sato, Ken Sakamoto, Akira Shigenaga, Tsubasa Inokuma, Takahiko Hara and Akira Otaka
  • Journal Title: Bioorganic & Medicinal Chemistry Volume: 23 Issue: 17 Pages: 5909-5914
  • DOI: 10.1016/j.bmc.2015.06.064
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] LIM homeobox transcription factor Lhx2 inhibits skeletal muscle differentiation in part via transcriptional activation of Msx1 and Msx2 (2015)
  • Author(s): Kodaka Y, Tanaka K, Kitajima K, Tanegashima K, Matsuda R, Hara T.
  • Journal Title: Exp Cell Res. Volume: 331 Pages: 309-319
  • Peer Reviewed
• [Journal Article] CXCL14 antagonizes the CXCL12-CXCR4 signaling axis (2014)
  • Author(s): Hara T, Tanegashima K.
  • Journal Title: Biomol Concepts. Volume: 5 Issue: 2 Pages: 167-173
  • DOI: 10.1515/bmc-2014-0007
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] 『ケモカインと幹細胞』 CXCL12-CXCR4 軸を介した幹細胞誘引の調節因子 (2014)
  • Author(s): 原 孝彦, 種子島 幸祐
  • Journal Title: 日本薬理学雑誌 Volume: 144 Pages: 4-7
  • NAID: 130004437204
• [Journal Article] CXCL14 is a natural inhibitor of the CXCL12-CXCR4 signaling axis (2013)
  • Author(s): K. Tanegashima, K. Suzukia, Y. Nakayama, K. Tsuji, A. Shigenaga, A. Otaka, and T. tiara
  • Journal Title: FEBS Letters Volume: 587 Issue: 12 Pages: 1731-1735
  • DOI: 10.1016/j.febslet.2013.04.046
  • Peer Reviewed
• [Journal Article] Dimeric peptides of the C-terminal region of CXCL14 function as CXCL12 inhibitors (2013)
  • Author(s): K. Tanegashima, K. Tsuji, K. Su zuki, A. Shigenaga, A. Otaka, and T. Hara
  • Journal Title: FEBS Letters Volume: 587 Issue: 23 Pages: 3770-3775
  • DOI: 10.1016/j.febslet.2013.10.017
  • Peer Reviewed
• [Presentation] β-ヒドロキシ酪酸によるHDACの阻害はGlut1の発現上昇を介して脳グルコース恒常性に寄与する. (2015)
  • Author(s): 種子島幸祐, 佐藤由紀子, 西藤 泰昌, 相垣 敏郎, 原 孝彦.
  • Organizer: 第38回日本分子生物学会年会,
  • Place of Presentation: 神戸ポートピアホテル(兵庫県神戸市)
  • Year and Date: 2015-12-01
• [Presentation] Gタンパク質共役型レセプターLatrophilin-2はプラコードと神経堤細胞の相互作用に関与する. (2015)
  • Author(s): 横手夏美, 種子島幸祐, 鈴木マリアンナ由乃, 道上達男, 原 孝彦.
  • Organizer: 第38回日本分子生物学会年会,
  • Place of Presentation: 神戸ポートピアホテル(兵庫県神戸市)
  • Year and Date: 2015-12-01
• [Presentation] ケモカインCXCL14は癌細胞のヘパラン硫酸に高親和性で結合する. (2015)
  • Author(s): 髙橋伶奈, 種子島幸祐, 辻 耕平, 重永 章, 大髙 章, 原 孝彦.
  • Organizer: 第38回日本分子生物学会年会,
  • Place of Presentation: 神戸ポートピアホテル(兵庫県神戸市)
  • Year and Date: 2015-12-01
• [Presentation] Functional interaction between Latrophilin-2 and Teneurin-2/4 in the migration of neural crest cells. (2015)
  • Author(s): Tanegashima K., Yokote N., Suzuki M. Y., Michiue T., Hara T.
  • Organizer: 第48回日本発生生物学会年会,
  • Place of Presentation: 筑波国際会議場 （茨城県つくば市）
  • Year and Date: 2015-06-02
• [Presentation] One-pot chemical synthesis of CXCL14 using N-sulfanylethylanilide peptide (2014)
  • Author(s): Tsuji K., Sato K., Sakamoto, K., Tanegashima K., Shigenaga A., Inokuma T., Hara T., Otaka A.
  • Organizer: 第51回ペプチド討論会
  • Place of Presentation: 徳島大学大塚講堂 （徳島県徳島市）
  • Year and Date: 2014-10-22 – 2014-10-24
• [Presentation] Modulation of CXCR4-mediated signaling pathway by CXCL14. (2014)
  • Author(s): Tanegashima K., Ohta S., K. Suzuki, K. Tsuji, A. Shigenaga, A. Otaka, T. Hara.
  • Organizer: CBSM International Joint Symposium
  • Place of Presentation: Andong, Korea.
  • Year and Date: 2014-06-20 – 2014-06-21
• [Presentation] Latrophilin-2 is involved in the migration and differentiation of neural crest cells. (2014)
  • Author(s): Tanegashima K., Suzuki M. Y., Suzuki K., Michiue T., Hara T.
  • Organizer: 第47回日本発生生物学会年会,
  • Place of Presentation: ウインク愛知 (愛知県名古屋市)
  • Year and Date: 2014-05-28 – 2014-05-30
• [Presentation] ケモカインCXCL14は、CXCL12-CXCR4シグナル経路を阻害する
  • Author(s): 種子島 幸祐
  • Organizer: 第三十六回 分子生物学会
  • Place of Presentation: 神戸ポートアイランド
• [Presentation] オーファンGタンパク質共役型レセプターLatrophilin-2の神経堤細胞遊走への関与
  • Author(s): 鈴木 マリアンナ由乃,種子島 幸祐, 鈴木 健司, 道上 達男, 原 孝彦
  • Organizer: 第三十六回 分子生物学会
  • Place of Presentation: 神戸ポートアイランド
• [Presentation] Identification of The CXCL14 Receptor: CXCL14 is a Natural Inhibitor of The CXCL12/CXCR4 Axis.
  • Author(s): 種子島 幸祐, 鈴木 健司, 長澤 丘司, 原 孝彦
  • Organizer: 第十一回 幹細胞シンポジウム
  • Place of Presentation: 東京大学 伊藤国際学術研究センター
• [Remarks] 公益財団法人東京都医学総合研究所・幹細胞プロジェクト
  • URL: http://www.igakuken.or.jp/project/detail/stem-cell.html
• [Remarks] 公益財団法人東京都医学総合研究所 幹細胞プロジェクト
  • URL: http://www.igakuken.or.jp/stem-cell/