愛知医科大学 医学部 感染・免疫学講座２（旧寄生虫学）です。

免疫学分野 過去の業績(～201４年)

2014年

• Sachiko Akashi-Takamura.  敗血症性ショックに関与するToll-like receptorの機能The function of Toll-like receptor which participates in a septic shock. 　Antibiotics & Chemotherapy　(化学療法の領域). 2014;30(4):40-7.
• Tanimura N, Saitoh SI, Ohto U, Akashi-Takamura S, Fujimoto Y, Fukase K, Shimizu T, Miyake K. The attenuated inflammation of MPL is due to the lack of CD14-dependent tight dimerization of the TLR4/MD2 complex at the plasma membrane. Int Immunol. 2014;26(6):307-14.  
• 森田奈央子，高村(赤司)祥子．TLR4応答におけるRP105/MD-1の役割 臨床免疫・アレルギー科．2014；62(2)：217-22.
• 中島昭奈，高村(赤司)祥子．スフィンゴシン１リン酸の生体における機能について．エンドトキシン・自然免疫研究17．2014;49-52.

2013年

• Kayagaki N, Wong MT, Stowe IB, Ramani SR, Gonzalez LC, Akashi-Takamura S,　Miyake K, Zhang J, Lee WP, Muszyński A, Forsberg LS, Carlson RW, Dixit VM. Noncanonical inflammasome activation by intracellular LPS independent of TLR4. Science. 2013; 341(6151):1246-9. 
• Deguchi A, Tomita T, Omori T, Komatsu A, Ohto U, Takahashi S, Tanimura N, Akashi-Takamura S, Miyake K, Maru Y. Serum amyloid A3 binds MD-2 to activate p38 and NF-κB pathways in a MyD88-dependent manner. J.Immunol. 2013;91(4):1856-64.
• Hiratsuka S, Ishibashi S, Tomita T, Watanabe A, Akashi-Takamura S, Murakami M, Kijima H, Miyake K, Aburatani H, Maru Y. Primary tumours modulate innate immune signalling to create pre-metastatic vascular hyperpermeability foci. Nat. Commun. 2013;4:1853.
• Kondo Y, Ikeda K, Tokuda N, Nishitani C, Ohto U, Akashi-Takamura S, Ito Y, Uchikawa M, Kuroki Y, Taguchi R, Miyake K, Zhang Q, Furukawa K, Furukawa K. TLR4-MD-2 complex is negatively regulated by an endogenous ligand, globotetraosylceramide. Proc. Natl. Acad. Sci. U.S.A. 2013;110(12):4714-9.
• Yamakawa N, Ohto U, Akashi-Takamura S, Takahashi K, Saitoh S, Tanimura N, Suganami T, Ogawa Y, Shibata T, Shimizu T, Miyake K. Human TLR4 polymorphism D299G/T399I alters TLR4/MD-2 conformation and response to a weak ligand monophosphoryl lipid A. Int.Immunol. 2013;1:45-52.
  　

2012年

• Ohto U, Yamakawa N, Akashi-Takamura S, Miyake K, Shimizu T. Structural analyses of human Toll-like receptor 4 polymorphisms D299G and T399I. J.Biol.Chem. 2012;287(48): 40611-7.
• Doronin K, Flatt JW, Di Paolo NC, Khare R, Kalyuzhniy O, Acchione M, Sumida JP, Ohto U, Shimizu T, Akashi-Takamura S, Miyake K, MacDonald JW, Bammler TK, Beyer RP, Farin FM, Stewart PL, Shayakhmetov DM. Coagulation factor X activates innate immunity to human species C adenovirus. Science. 2012;338(6108):795-8.
• Honda H, Nagai Y, Matsunaga T, Saitoh S, Akashi-Takamura S, Hayashi H, Fujii I, Miyake K, Muraguchi A, Takatsu K. Glycyrrhizin and isoliquiritigenin suppress the LPS sensor toll-like receptor 4/MD-2 complex signaling in a different manner. J. Leukoc. Biol. 2012; 91(6):967-76.
• Shibata T, Takemura N, Motoi Y, Goto Y, Karuppuchamy T, Izawa K, Li X, Akashi-Takamura S, Tanimura N, Kunisawa J, Kiyono H, Akira S, Kitamura T, Kitaura J, Uematsu S, Miyake K PRAT4A-dependent expression of cell surface TLR5 on neutrophils, classical monocytes and dendritic cells. Int. Immunol. 2012;24(10):613-23.

2011年

• Shibata T, Motoi Y, Tanimura N, Yamakawa N, Akashi-Takamura S, Miyake K. Intracellular TLR4/MD-2 in macrophages sense Gram-negative bacteria and induces a unique set of LPS-dependent genes. Int. Immunol. 2011;8:503-1.

2010年

• Murata A, Okuyama K, Sakano S, Kajiki M, Hirata T, Yagita H, Zúñiga-Pflücker JC, Miyake K, Akashi-Takamura S, Moriwaki S, Niida S, Yoshino M, Hayashi S. A Notch ligand, Delta-like 1 functions as an adhesion molecule for mast cells. J Immunol. 2010;185(7):3905-12.

2008年

• Hiratsuka S, Watanabe A, Sakurai Y, Akashi-Takamura S, Ishibashi S, Miyake K, Shibuya M, Akira S, Aburatani H, Maru Y. The S100A8-serum amyloid A3-TLR4 paracrine cascade establishes a pre-metastatic phase. Nat Cell Biol2008;10,1349-55.
• Kiyokawa T, Akashi-Takamura S, Shibata T, Matsumoto F, Nishitani C, Kuroki Y, Seto Y, Miyake K. A single base mutation in the PRAT4A gene reveals differential interaction of PRAT4A with Toll-like receptors. Int Immunol.  2008;20:1407-15.
• Shawkat S, Karima R, Tojo T, Tadakuma H, Saitoh S, Akashi-Takamura S, Miyake K, Funatsu T, Matsushima K. Visualization of the molecular dynamics of lipopolysaccharide on the plasma membrane of murine macrophages by total internal reflection fluorescence microscopy. J Biol Chem . 2008;283:22962-71.
• Tanimura N, Saitoh S, Matsumoto F, Akashi-Takamura S, Miyake K. Roles for LPS-dependent interaction and relocation of TLR4 and TRAM in TRIF-signaling. Biochem Biophys Res Commun. 2008;368:94-9.
• Matsumoto F, Saitoh S, Fukui R, Kobayashi T, Tanimura N, Konno K, Kusumoto Y, Akashi-Takamura S, Miyake K. Cathepsins are required for Toll-like receptor 9 responses. Biochem Biophys Res Commun. 2008;367: 693-9.
• Akashi-Takamura S, Miyake K. TLR accessory molecules. Curr Opin Immunol. 2008;20:420-5.
• 清川貴志, 高村(赤司)祥子, 三宅健介. 自然免疫系とアレルギー. アレルギーの臨床.  2008;28(3):183-7.

2007年

• Takahashi K, Shibata T, Akashi-Takamura S, Kiyokawa T, Wakabayashi Y, Tanimura N, Kobayashi T, Matsumoto F, Fukui R, Kouro T, Nagai Y, Takatsu K, Saitoh S, Miyake K. A protein associated with Toll-like receptor (TLR) 4 (PRAT4A) is required for TLR-dependent immune responses. J Exp Med. 2007;204:2963-76.
• 高村(赤司)祥子、高橋浩一郎、柴田琢磨、若林靖貴、三宅健介. TLR会合分子PRAT4Aによる病原体認識調節機構. 日本エンドトキシン研究会. エンドトキシン研究10 基礎と臨床の最新知見. 東京:医学図書出版. 2007:101-9.
• 清川貴志, 高村(赤司)祥子, 三宅健介. 感染症の病態におけるTLRとシグナル伝達機構. 化学療法の領域. 2007;23(10): 1547-53.
• 清川貴志, 高村(赤司)祥子, 三宅健介. Toll Like Receptorによるエンドトキシン認識とシグナル伝達機構. ICUとCCU. 2007;31(6):393-9.
• 高村(赤司)祥子. PRAT4A(Protein Associated with TLR4)による免疫応答制御機構. 消化器と免疫. 2007;44:17-21. 

2006年

• Wakabayashi Y, Kobayashi M, Akashi-Takamura S, Tanimura N, Konno K, Takahashi K, Ishii T, Mizutani T, Iba H, Kouro T, Takaki S, Takatsu K, Oda Y, Ishihama Y, Saitoh S, Miyake K. A protein associated with toll-like receptor 4 (PRAT4A) regulates cell surface expression of TLR4. J Immunol. 2006;177: 1772-9.
• Kobayashi M, Saitoh S, Tanimura N, Takahashi K, Kawasaki K, Nishijima M, Fujimoto Y, Fukase K, Akashi-Takamura S, Miyake K. Regulatory roles for MD-2 and TLR4 in ligand-induced receptor clustering. J Immunol. 2006;176: 6211-8.
• Akashi-Takamura S, Furuta T, Takahashi K, Tanimura N, Kusumoto Y, Kobayashi T, Saitoh S, Adachi Y, Doi T, Miyake K. Agonistic antibody to TLR4/MD-2 protects mice from acute lethal hepatitis induced by TNF-alpha. J Immunol. 2006;176:4244-51.
• Konno K, Wakabayashi Y, Akashi-Takamura S, Ishii T, Kobayashi M, Takahashi K, Kusumoto Y, Saitoh S, Yoshizawa Y, Miyake K. Commun A molecule that is associated with Toll-like receptor 4 and regulates its cell surface expression. Biochem Biophys Res. 2006;339:1076-82.
• Okamoto M, Oshikawa T, Tano T, Ahmed SU, Kan S, Sasai A, Akashi S, Miyake K, Moriya Y, Ryoma Y, Saito M, Sato M. Mechanism of anticancer host response induced by OK-432, a streptococcal preparation, mediated by phagocytosis and Toll-like receptor 4 signaling. J Immunother. 2006;29: 78-86.
• Tsuneyoshi N, Kohara J, Bahrun U, Saitoh S, Akashi S, Gauchat JF, Kimoto M, Fukudome K. Penta-acylated lipopolisaccharide binds to murine MD-2 but does not induce the oligomerization of TLR4 required for signal transduction. Cell Immunol. 2006;244:57-64.
• Akashi-Takamura S, Miyake K. Toll-like receptors (TLRs) and immune disorders. J Infect Chemother. 2006;12:233-40.
  　

2005年

• Nagaoka K, Takahara K, Tanaka K, Yoshida H, Steinman RM, Saitoh S, Akashi-Takamura S, Miyake K, Kang YS, Park CG, Inaba K. Association of SIGNR1 with TLR4-MD-2 enhances signal transduction by recognition of LPS in gram-negative bacteria. Int Immunol. 2005;17:827-36.
• Nagai Y, Kobayashi T, Motoi Y, Ishiguro K, Akashi S, Saitoh S, Kusumoto Y, Kaisho T, Akira S, Matsumoto M, Takatsu K, Miyake K. The radioprotective 105/MD-1 complex links TLR2 and TLR4/MD-2 in antibody response to microbial membranes. J Immunol. 2005;174:7043-9.
• 高村(赤司)祥子. TLRとそのシグナル－TLRと微生物認識. 日本臨床. 2005;63( Suppl4):102-8.
• 高村(赤司)祥子. エンドトキシンショックとTLR－TLRによるエンドトキシンの認識機構－. 炎症と免疫. 2005;13(1):37-44.

 

2004年

• Saitoh S, Akashi S, Yamada T, Tanimura N, Matsumoto F, Fukase K, Kusumoto S, Kosugi A, Miyake K. Ligand-dependent Toll-like receptor 4 (TLR4)-oligomerization is directly linked with TLR4-signaling. J Endotoxin Res. 2004;10:257-60.
• Saitoh S, Akashi S, Yamada T, Tanimura N, Kobayashi M, Konno K, Matsumoto F, Fukase K, Kusumoto S, Nagai Y, Kusumoto Y, Kosugi A, Miyake K. Lipid A antagonist, lipid IVa, is distinct from lipid A in interaction with Toll-like receptor 4 (TLR4)-MD-2 and ligand-induced TLR4 oligomerization. Int Immunol. 2004;16:961-9.
• Iwahashi M, Yamamura M, Aita T, Okamoto A, Ueno A, Ogawa N, Akashi S, Miyake K, Godowski PJ, Makino H. Expression of Toll-like receptor 2 on CD16+ blood monocytes and synovial tissue macrophages in rheumatoid arthritis. Arthritis Rheum. 2004;50:1457-67.
• Okamoto M, Oh EG, Oshikawa T, Furuichi S, Tano T, Ahmed SU, Akashi S, Miyake K, Takeuchi O, Akira S, Himeno K, Sato M, Ohkubo S. Toll-like receptor 4 mediates the antitumor host response induced by a 55-kilodalton protein isolated from Aeginetia indica L., a parasitic plant. Clin Diagn Lab Immunol . 2004;11:483-95.
• 赤司祥子. 得られた遺伝子（細胞表面分子）に対するモノクローナル抗体の作製. 高津聖志，三宅健介，山元弘，瀧伸介. 実験医学別冊（タンパク質研究のための抗体実験マニュアル）. 東京:羊土社. 2004: 168-80.
• 赤司祥子. CD14,TLR4,MD-2とLPSの相互作用. 臨床免疫. 2004;42(1):115-21.

2003年

• Akashi S, Saitoh S, Wakabayashi Y, Kikuchi T, Takamura N, Nagai Y, Kusumoto Y, Fukase K, Kusumoto S, Adachi Y, Kosugi A, Miyake K. Lipopolysaccharide interaction with cell surface Toll-like receptor 4-MD-2: higher affinity than that with MD-2 or CD14.  J Exp Med. 2003;198:1035-42.
• Dory D, Echchannaoui H, Letiembre M, Ferracin F, Pieters J, Adachi Y, Akashi S, Zimmerli W, Landmann R. Generation and functional characterization of a clonal murine periportal Kupffer cell line from H-2Kb -tsA58 mice. J Leukoc Biol. 2003;74:49-59.
• Hatakeyama J, Tamai R, Sugiyama A, Akashi S, Sugawara S, Takada H. Contrasting responses of human gingival and periodontal ligament fibroblasts to bacterial cell-surface components through the CD14/Toll-like receptor system. Oral Microbiol Immunol. 2003;18:14-23.
• Okamoto M, Oshikawa T, Tano T, Ohe G, Furuichi S, Nishikawa H, Ahmed SU, Akashi S, Miyake K, Takeuchi O, Akira S, Moriya Y, Matsubara S, Ryoma Y, Saito M, Sato M. Involvement of Toll-like receptor 4 signaling in interferon-gamma production and antitumor effect by streptococcal agent OK-432. J Natl Cancer I. 2003;95:316-26.
• 高橋浩一郎、赤司祥子、三宅健介. 分子細胞治療 エンドトキシン認識機構. 2003; 2(5):592-597.

2002年

• Miyake K, Nagai Y, Akashi S, Nagafuku M, Ogata M, Kosugi A. Essential role of MD-2 in B-cell responses to lipopolysaccharide and Toll-like receptor 4 distribution. J Endotoxin Res. 2002;8:449-52.
• Hijiya N, Miyake K, Akashi S, Matsuura K, Higuchi Y, Yamamoto S. Possible involvement of toll-like receptor 4 in endothelial cell activation of larger vessels in response to lipopolysaccharide. Pathobiology. 2002;70:18-25.
• Ando I, Tsukumo Y, Wakabayashi T, Akashi S, Miyake K, Kataoka T, Nagai K. Safflower polysaccharides activate the transcription factor NF-kappa B via Toll-like receptor 4 and induce cytokine production by macrophages. Int Immunopharmacol. 2002;2:1155-62.
• Tada H, Nemoto E, Shimauchi H, Watanabe T, Mikami T, Matsumoto T, Ohno N, Tamura H, Shibata K, Akashi S, Miyake K, Sugawara S, Takada H. Saccharomyces cerevisiae- and Candida albicans-derived mannan induced production of tumor necrosis factor alpha by human monocytes in a CD14- and Toll-like receptor 4-dependent manner. Microbiol Immunol. 2002;46: 503-12.
• Ishida I, Kubo H, Suzuki S, Suzuki T, Akashi S, Inoue K, Maeda S, Kikuchi H, Sasaki H, Kondo T. Hypoxia diminishes toll-like receptor 4 expression through reactive oxygen species generated by mitochondria in endothelial cells. J Immunol. 2002;169:2069-75.
• Kitamura H, Kanehira K, Shiina T, Morimatsu M, Jung BD, Akashi S, Saito M. Bacterial lipopolysaccharide induces mRNA expression of an IkappaB MAIL through toll-like receptor 4. J Vet Med Sci. 2002;64:419-22.
• Nagai Y, Akashi S, Nagafuku M, Ogata M, Iwakura Y, Akira S, Kitamura T, Kosugi A, Kimoto M, Miyake K. Essential role of MD-2 in LPS responsiveness and TLR4 distribution. Nat Immunol. 2002;3:667-72.
• Nagai Y, Shimazu R, Ogata H, Akashi S, Sudo K, Yamasaki H, Hayashi S, Iwakura Y, Kimoto M, Miyake K. Requirement for MD-1 in cell surface expression of RP105/CD180 and B-cell responsiveness to lipopolysaccharide. Blood. 2002;99:1699-705.
• Tamai R, Sakuta T, Matsushita K, Torii M, Takeuchi O, Akira S, Akashi S, Espevik T, Sugawara S, Takada H. Human gingival CD14(+) fibroblasts primed with gamma interferon increase production of interleukin-8 in response to lipopolysaccharide through up-regulation of membrane CD14 and MyD88 mRNA expression. Infect Immun. 2002;70:1272-8.
• 赤司祥子, 三宅 健介. MD-2. 分子細胞治療. 東京:先端医学社. 2002:1(3); 349-51.

2001年

• Akashi S, Nagai Y, Ogata H, Oikawa M, Fukase K, Kusumoto S, Kawasaki K, Nishijima M, Hayashi S, Kimoto M, Miyake K. Human MD-2 confers on mouse Toll-like receptor 4 species-specific lipopolysaccharide recognition. Int Immunol. 2001;13:1595-9.
• Kawasaki K, Akashi S, Shimazu R, Yoshida T, Miyake K, Nishijima M. Involvement of TLR4/MD-2 complex in species-specific lipopolysaccharide-mimetic signal transduction by Taxol. J Endotoxin Res. 2001;7:232-6.
• Yang S, Sugawara S, Monodane T, Nishijima M, Adachi Y, Akashi S, Miyake K, Hase S, Takada H. Micrococcus luteus teichuronic acids activate human and murine monocytic cells in a CD14- and toll-like receptor 4-dependent manner. Infect Immun. 2001;69:2025-30.
• Sugawara S, Yang S, Iki K, Hatakeyama J, Tamai R, Takeuchi O, Akashi S, Espevik T, Akira S, Takada H. Monocytic cell activation by Nonendotoxic glycoprotein from Prevotella intermedia ATCC 25611 is mediated by toll-like receptor 2. Infect Immun. 2001;69:4951-7.
• Yang S, Tamai R, Akashi S, Takeuchi O, Akira S, Sugawara S, Takada H. Synergistic effect of muramyldipeptide with lipopolysaccharide or lipoteichoic acid to induce inflammatory cytokines in human monocytic cells in culture. Infect Immun. 2001;69:2045-53.
• 赤司祥子, 三宅健介. LPS識別におけるToll like receptorと MD分子. Annual Review 免疫. 2001:94-102.
• 赤司祥子, 三宅健介. Toll-like receptorを介するシグナル伝達機構－MDタンパクの役割－. 臨床免疫. 2001;36(4):515-24.
• 赤司祥子, 三宅健介. 自然免疫におけるMD分子によるLPS認識制御機構. 実験医学.   2001;19(18):2376-80.

2000年

• Miyake K, Ogata H, Nagai Y, Akashi S, Kimoto M. Innate recognition of lipopolysaccharide by Toll-like receptor 4/MD-2 and RP105/MD-1. J Endotoxin Res. 2000;6:389-91.
• Tapping RI, Akashi S, Miyake K, Godowski PJ, Tobias PS. Toll-like receptor 4, but not toll-like receptor 2, is a signaling receptor for Escherichia and Salmonella lipopolysaccharides. J Immunol. 2000;165:5780-7.
• Jiang Q, Akashi S, Miyake K, Petty HR. Lipopolysaccharide induces physical proximity between CD14 and toll-like receptor 4 (TLR4) prior to nuclear translocation of NF-kappa B. J Immunol. 2000;165:3541-4.
• Ogata H, Su I, Miyake K, Nagai Y, Akashi S, Mecklenbrauker I, Rajewsky K, Kimoto M, Tarakhovsky A. The toll-like receptor protein RP105 regulates lipopolysaccharide signaling in B cells. J Exp Med. 2000;192:23-9.
• Tabeta K, Yamazaki K, Akashi S, Miyake K, Kumada H, Umemoto T, Yoshie H. Toll-like receptors confer responsiveness to lipopolysaccharide from Porphyromonas gingivalis in human gingival fibroblasts. Infect Immun. 2000; 68:3731-5.
• Nomura F, Akashi S, Sakao Y, Sato S, Kawai T, Matsumoto M, Nakanishi K, Kimoto M, Miyake K, Takeda K, Akira S. Cutting edge:Endotoxin tolerance in mouse peritoneal macrophages correlates with down-regulation of surface toll-like receptor 4 expression. J Immunol. 2000;164:3476-9.
• Akashi S, Shimazu R, Ogata H, Nagai Y, Takeda K, Kimoto M, Miyake K. Cutting edge:Cell surface expression and lipopolysaccharide signaling via the toll-like receptor 4-MD-2 complex on mouse peritoneal macrophages. J Immunol. 2000;164:3471-5.
• Akashi S, Ogata H, Kirikae F, Kirikae T, Kawasaki K, Nishijima M, Shimazu R, Nagai Y, Fukudome K, Kimoto M, Miyake K. Commun  Regulatory roles for CD14 and phosphatidylinositol in the signaling via toll-like receptor 4-MD-2. Biochem Biophys Res. 2000;268:172-7.
• Kawasaki K, Akashi S, Shimazu R, Yoshida T, Miyake K, Nishijima M. Mouse toll-like receptor 4.MD-2 complex mediates lipopolysaccharide-mimetic signal transduction by Taxol. J Biol Chem. 2000;275:2251-4.

1999年

• Shimazu R, Akashi S, Ogata H, Nagai Y, Fukudome K, Miyake K, Kimoto M. MD-2, a molecule that confers lipopolysaccharide responsiveness on Toll-like receptor 4. J Exp Med. 1999;189:1777-82.
• 赤司祥子, 三宅健介. 自然免疫におけるToll-like receptor (TLR)ファミリーの意義. Molecular Medicine. 1999;36(5):488-97.
• 赤司祥子, 島津倫太郎, 三宅健介. リポ多糖レセプターTLR4-MD-2の解明. 細胞工学.   1999;18(7):1006-8.

1998年

• Miura Y, Shimazu R, Miyake K, Akashi S, Ogata H, Yamashita Y, Narisawa Y, Kimoto M. RP105 is associated with MD-1 and transmits an activation signal in human B cells. Blood. 1998;92:2815-22.
• Miyake K, Shimazu R, Kondo J, Niki T, Akashi S, Ogata H, Yamashita Y, Miura Y, Kimoto M. Mouse MD-1, a molecule that is physically associated with RP105 and positively regulates its expression. J Immunol. 1998;161:1348-53.
• 松原紳一, 赤司祥子, 内藤恵子, 中原快明, 林真一郎. 血液浄化療法併用にて救命し得た重症Legionella micdadei肺炎の１例. 日本胸部疾患学会雑誌. 1998;36(10):886-890.

1997年

• 中原快明, 河島通博, 藤澤伸光, 内藤恵子, 赤司祥子, 林真一郎. 肺血栓塞栓症における胸部造影ＣＴの診断的有用性について. 日本胸部疾患学会雑誌. 1997;35:300-5.
• 赤司祥子, 富永正樹, 内藤恵子, 藤澤伸光, 中原快明, 日浦研哉, 林真一郎. アセトアミノフェンによる薬剤誘起性肺臓炎の2例. 日本胸部疾患学会雑誌. 1997;35(9):974-9.

1996年

• 赤司祥子, 小山孝則, 岩切龍一, 藤本一真, 松岡由香里, 松井敏幸.   経過中common variable immunodeficiencyが顕在化した潰瘍性大腸炎の1例. 日本消化器病学会雑誌. 1996;93(6):423-7.