Analysis of mechanism of IL-12 induction from macrophage stimulated by the mutant of Escherichia coli enterotoxin

• Project/Area Number: 18590440
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Bacteriology (including Mycology)
• Research Institution: Fujita Health University
• Principal Investigator: TSUJI Takao Fujita Health University, 医学部, 教授 (60171998)
• Project Period (FY): 2006 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥4,100,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥600,000); Fiscal Year 2008: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2007: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2006: ¥1,500,000 (Direct Cost: ¥1,500,000)
• Keywords: 粘膜アジュバント / 易熱性下痢毒素 / マクロファージ / コレラ毒素 / 毒素原性大腸菌 / IL-12 / Th1 / Th2バランス

Research Abstract

ETECのLTの変異体(mLT)は、志賀毒素2または死菌BCGに対するTh2またはTh1系T細胞を活性化すること、mLTはマクロファージ(Mφ)からのIL-12とTNFα産生を促進することを明らかにした。上昇したTNFαはIL-12産生促進の上流に存在していたが、NF-κおよびJNK経路の活性化はなかった。そこで、CREBを介してTh2系T細胞を活性化が予想されているコレラ毒素とmLTを比較検討し、mLT特有の細胞内情報伝達機構の解析を進めている。

Research Products

• [Journal Article] Lincomycin-induced over-expression of mature recombinant cholera toxin B subunit and the holotoxin in Escherichia coli (2009)
  • Author(s): Arimitsu H, Tsukamoto K, Ochi S, Sasaki S, Kato K, Taniguchi K, Oguma K and Tsuji T.
  • Journal Title: Protein Expression and Purification (in press)
  • Peer Reviewed
• [Journal Article] Protection of mice from Shiga toxin-2 toxemia by mucosal vaccine of Shiga toxin 2B-His with Escherichia coli enterotoxin (2008)
  • Author(s): Tsuji T, Shimizu T, Sasaki K, Shimizu Y, Tsukamoto K, Arimitsu H, Ochi S, Sugiyama S, Taniguchi K, Neri P, Mori H.
  • Journal Title: Vaccine 26 Pages: 469-476
  • Peer Reviewed
• [Journal Article] Molecular typing and epidemiology of non-polio enteroviruses isolated from Yunnan Province, the People's Republic of China (2008)
  • Author(s): Bingium T, Yoshida H, Lin , Tsuji T, Shimizu H, Miyamura T.
  • Journal Title: J. Med. Virol 80 Pages: 670-679
  • Peer Reviewed
• [Journal Article] Identification of the receptor-binding sites in the carboxyl-terminal half of the heavy chain of botulinum neurotoxin types C and D. (2008)
  • Author(s): Tsukamoto, K., Kozai, Y., Ihara, H., Kohda, T., Mukamoto, M., Tsuji, T. and Kozaki, S.
  • Journal Title: Microb Pathog 44 Pages: 484-493
  • Peer Reviewed
• [Journal Article] A nasal vaccine comprising B-subunit derivative of Shiga toxin 2 for cross-protection against Shiga toxin types 1 and 2 (2008)
  • Author(s): Tsuji T, Shimizu T, Sasaki K, Shimizu T, Tsukamoto K, Arimitsu H, Ochi S, Taniguchi K, Noda M, Neri P, and Mori H.
  • Journal Title: Vaccine 26 Pages: 2092-2099
  • Peer Reviewed
• [Journal Article] Intranasal immunization of mutant toxic shock syndrome toxin 1elicits systemic and mucosal immune response against Staphylococcus aureus infection (2008)
  • Author(s): Narita K, Dong-Liang H ; Tsuji T, Nakane A.
  • Journal Title: FEMS Immunol. Med. Microbiol 52 Pages: 389-396
  • Peer Reviewed
• [Journal Article] Molecular properties of each subcomponent in Clostridium botulinum type B haemagglutinin complex (2008)
  • Author(s): Arimitsu H, Sakaguch Yi, Lee J. C, Ochi S, Tsukamoto K, Yamamoto Y, Ma S, Tsuji T, and Oguma. K.
  • Journal Title: Microb Pathog 45 Pages: 142-9
  • Peer Reviewed
• [Journal Article] Protection of mice from Shiga toxin-2 toxemia by mucosal vaccine of Shiga toxin 2B-His with Escherichia coli enterotoxin. (2008)
  • Author(s): Tsuji T., et al.
  • Journal Title: Vaccine 26 Pages: 469-476
  • Peer Reviewed
• [Journal Article] A nasal vaccine comprising B-subunit derivative of Shiga toxin 2 for cross-protection against Shiga toxin types 1 and 2. (2008)
  • Author(s): Tsuji T., et al.
  • Journal Title: Vaccine 26 Pages: 2092-2099
  • Peer Reviewed
• [Journal Article] Molecular typing and epidemiology of non-polio enteroviruses isolated from Yunnan Province, the People's Republic of China. (2008)
  • Author(s): . Bingium T, Yoshida H, Lin, Tsuji T, et al.
  • Journal Title: J. Med. Virol. 80 Pages: 670-678
  • Peer Reviewed
• [Journal Article] Protection of mice from Shiga toxin-2 toxemia by mucosal vaccine of Shiga toxin 2B-His with Escherichia coli enterotoxin. (2008)
  • Author(s): Tsuji T., et. al.
  • Journal Title: Vaccine 26 Pages: 469-476
  • Peer Reviewed
• [Journal Article] A nasal vaccine comprising B-subunit derivative of Shiga toxin 2 for cross-protection against Shiga toxin types 1 and 2. (2008)
  • Author(s): Tsuji T., et. al.
  • Journal Title: Vaccine (In press)
  • Peer Reviewed
• [Journal Article] Identification of the receptor-binding sites in the carboxyl-terminal half of the heavy chain of botulinum neurotoxin types C and D. (2008)
  • Author(s): Tsukamoto, K., a and Tsuji T., et. al.
  • Journal Title: Microbial. Pathogenesis (In press)
  • Peer Reviewed
• [Journal Article] C terminal half fragment (50 kDa) of heavy chain components of Clostridium botulinum type C and D neurotoxins can be used as an effective vaccine (2007)
  • Author(s): Lee JC, Hwang HJ, Sakaguchi Y, Tsuji T, Watanabe T, Ohyama T, Tsuchiya T, Oguma K.
  • Journal Title: Microbiol Immunol 51 Pages: 445-455
  • NAID: 10020280881
  • Peer Reviewed
• [Journal Article] A mutant of Escherichia coli enterotoxin inducing a specific Thl-type of T cells to varicella-zoster vaccine enhances the production of IL-12 by IFNgamma-stimulated macrophages (2006)
  • Author(s): Shimizu T, Sasaki K, Kato M, Tsuji T., et.al.
  • Journal Title: Vaccine 24 Pages: 3719-3726
  • Peer Reviewed
• [Journal Article] Cleavage specificity of the serine protease of Aeromonas sobria,a member of the kexin family of subtilases (2006)
  • Author(s): Kobayashi H, Takahashi E, Oguma K, Fujii Y, Yamanaka H, Negishi T, Arimoto- Tsuji T, et.al.
  • Journal Title: FEMS Microbiology Letters 256 Pages: 165-170
  • Peer Reviewed
• [Journal Article] Enhanced mucosal immunogenicity of prion protein following fusion with B subunit of Escherichia coli heat-labile enterotoxin (2006)
  • Author(s): Yamanaka H, Ishibashi D, Yamaguchi N, Yoshikawa D, Nakamura R, Okimura N, Arakawa T, Tsuji T, Katamine S, Sakaguchi. S.
  • Journal Title: Vaccine 24(15) Pages: 2815-23
  • Peer Reviewed
• [Journal Article] Mutant Escherichia coli enterotoxin as a mucosal adjuvant induces specific Th1 responses of CD4(+) and CD8(+) T cells to nasal killed-bacillus calmette-guerin in mice (2006)
  • Author(s): Takahashi H, Sasaki K, Takahashi M, Shigemori N, Honda S, Arimitsu H, Ochi S, Ohara N, Tsuji T.
  • Journal Title: Vaccine 24(17) Pages: 3591-8
  • Peer Reviewed
• [Journal Article] Isolation of a human antibody with strong neutralizing activity against diphtheria toxin (2006)
  • Author(s): Kakita M, Takahashi T, Komiya T. Iba Y, Tsuji T, Kurosawa Y, Takahashi M.
  • Journal Title: Infect. Immun 74 Pages: 3682-3683
  • Peer Reviewed
• [Journal Article] A mutant of Escherichia coli enterotoxin inducing a specific Thl-type of T cells to varicella-zoster vaccine enhances the production of IL-12 by IFNgamma-stimulated macrophages. (2006)
  • Author(s): Shimizu T, Sasaki K, Tsuji, T et al.
  • Journal Title: Vaccine 24 Pages: 3719-26
• [Journal Article] Cleavage specificity of the serine protease of Aeromonas sobria,a member of the kexin family of subtilases. (2006)
  • Author(s): Kobayashi H, Tsuji, T et al.
  • Journal Title: FEMS Microbiology Letters 256 Pages: 165-70
• [Journal Article] Enhanced mucosal immunogenicity of prion protein following fusion with B subunit of Escherichia coli heat-labile enterotoxin. (2006)
  • Author(s): Yamanaka H, Tsuji, T et al.
  • Journal Title: Vaccine 24 Pages: 2815-23
• [Journal Article] Mutant Escherichia coli enterotoxin as a mucosal adjuvant induces specific Thl responses of CD4(+)and CD8(+)T cells to nasal killed-bacillus calmette-guerin in mice. (2006)
  • Author(s): Takahashi H, Tsuji, T et al.
  • Journal Title: Vaccine 24 Pages: 3591-8
• [Journal Article] Isolation of a human antibody with strong neutralizing activity against disphtheria toxin. (2006)
  • Author(s): Kakita M, Tsuji, T et al.
  • Journal Title: Infect. Immun. 74 Pages: 3682-3
• [Presentation] Construction of LM-induced expression system of CT b subunit in E. coli (2008)
  • Author(s): Arimitus H, Tsuji T, et al.
  • Organizer: The 43th Joint Meeting of the US-Japan Cholera and other Bacterial Enteric Infections Panel Fukuoka
  • Place of Presentation: 博多市、福岡
  • Year and Date: 2008-11-17
• [Presentation] Construction of lincomycin-induced expression system of cholera toxin B subunit in Escherichia coli (2008)
  • Author(s): Arimitsu H, Tsukamoto K, Ochi S, Keiko K and Tsuji T.
  • Organizer: 43rd U.S.-Japan Cholera & Other bacterial Enteric Infections Joint Panel Meeting
  • Place of Presentation: Fukuoka
• [Presentation] Complete Nucleotide Sequence of Heat-Labile and Heat-Stable Enterotoxin-Encoding Plasmid of Enterotoxigenic Escherichia coliH10407 (2007)
  • Author(s): Ochi S, Tsuji T, et. al.
  • Organizer: The 42th Joint Meeting of the US-Japan Cholera and other Bacterial Enteric Infections Panel(Texas, U.S.A)
  • Place of Presentation: Austin in America
  • Year and Date: 2007-12-11
• [Presentation] Complete Nucleotide Sequence of Heat-Labile and Heat-Stable Enterotoxin- Encoding Plasmid of Enterotoxigenic Escherichia coli H10407 (2007)
  • Author(s): Ochi S, Arimitsu H, Tsukamoto K, Ohtani K, Sasaki K, Shigemori N, Kato M, Shimizu T and Tsuji T.
  • Organizer: The 42th Joint Meeting of the US-Japan Cholera and other Bacterial Enteric Infections Panel (Austin). Formal poster session
  • Place of Presentation: Hyatt Regency Austin, 208 Barton Springs Road, Austin, Texas, USA
• [Book] 標準微生物学第10版(山西弘一、平松啓一、中込治編)細菌の病原因子 (2009)
  • Author(s): 辻孝雄
  • Total Pages: 7
  • Publisher: 医学書院発行
• [Book] 標準微生物学第10版(山西弘一, 平松啓一, 中込 治編) (2009)
  • Author(s): 辻 孝雄
  • Publisher: 医学書院
• [Book] 病原体等安全取り扱い・管理指針 (2008)
  • Author(s): 荒川宣親、江崎孝行、岡本敬の介、辻孝雄、渡辺治雄、他13名
  • Total Pages: 11
  • Publisher: 日本細菌学会発行
• [Book] 標準微生物学第10版(山西弘一、平松啓一、中込 治編) (2008)
  • Author(s): 辻 孝雄
  • Publisher: 医学書院(印刷中)