Analysis of biomarker for septic shock

• Project/Area Number: 20592132
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Emergency medicine
• Research Institution: University of Occupational and Environmental Health, Japan
• Principal Investigator: YAMASHITA Uki University of Occupational and Environmental Health, Japan, 医学部, 名誉教授 (00028680)
• Co-Investigator(Kenkyū-buntansha): YOSHIDA Yasuhiro 産業医科大学, 医学部, 准教授 (10309958) ; SUGIURA Tsutomu 産業医科大学, 産業医学研究支援施設, 准教授 (40131924)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2010: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2009: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2008: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
• Keywords: Septic shock / プロスタグランジン / PG合成酵素ノックアウトマウス / Septic Shock / マクロファージ / 免疫応答 / Th1, Th2

Research Abstract

We analyzed the role of prostaglandin (PG) in acute inflammatory reactions and the following immune responses using PG synthetase knockout (KO) mice. The production of cytokine from LPS-stimulated macrophages was decreased in PG-KO mice in comparison with wild type (WT) mice. On the other hand, the serum cytokine level from LPS-treated mice was higher in PG-KO mice than WT mice. In the LPS-challenged mice, serum GOT level was decreased in PG-KO mice. However, GPT level was equal between PG-KO and WT mice. The function of helper T cells after immunization with protein antigens in PG-KO mice was different from that of WT mice. Taken together, these results suggest that PG played an important role for the regulation of inflammatory and immune responses such as cytokine productions.

Research Products

• [Journal Article] Apoptosis induction through proteasome inhibitory activity of cucurbitacin D in human T-cell leukemia. (2011)
  • Author(s): Ding N., Yamashita U., Matsuoka H., Sugiura T., Tsukada J., Noguchi J., Yoshida Y.
  • Journal Title: Cancer (in press)
  • Peer Reviewed
• [Journal Article] Stimulation of IFN-gamma production by garlic lectin in mouse spleen cells : Involvement of IL-12 via activation of p38 MAPK and ERK in macrophages. (2011)
  • Author(s): Dong Q., Sugiura T., Toyohira Y., Yoshida Y., Yanagihara N., Karasaki Y.
  • Journal Title: Phytomedicine 18 Pages: 309-316
  • Peer Reviewed
• [Journal Article] Apoptosis induction through proteasome inhibitory activity of cucurbitacin D inhuman T-cell leukemia. (2011)
  • Author(s): Ding, N., Yamashita, U., Sugiura, T., Yoshida Y., et al.
  • Journal Title: Cancer Volume: In press
  • Peer Reviewed
• [Journal Article] Stimulation of IFN-gamma production by garlic lectin in mouse spleen cells : Involvement of IL-12 via activation of p38 MAPK and ERK in macrophages. (2011)
  • Author(s): Dong, Q., Sugiura, T., Yoshida Y., et al.
  • Journal Title: Phytomedicine Volume: 18 Pages: 309-316
  • Peer Reviewed
• [Journal Article] Thymocytes are activated by toluene inhalation through the transcription factors NF-κB, STAT5 and NF-AT. (2010)
  • Author(s): Liu JQ., Yoshida Y., Kunugita N., Noguchi J., Sugiura T., Ding N., Arashidani K., Fujimaki H., Yamashita U.
  • Journal Title: Journal of Applied Toxicology 30 Pages: 656-660
  • Peer Reviewed
• [Journal Article] Thymocytes are activated by toluene inhalation through the transcription factors NF-κ B, STAT5 and NF-AT. (2010)
  • Author(s): Liu, JQ., Yoshida Y., Sugiura T., Yamashita U., et al.
  • Journal Title: Journal of Applied Toxicology Volume: 30 Pages: 656-660
  • Peer Reviewed
• [Journal Article] An indoor air pollutant 2-ethyl-hexanol activates CD4 cells. (2009)
  • Author(s): Yoshida Y., Liu J.Q., Sugiura T., Ishidao T., Ueno S., Yanagita H., Fueta Y., Kunugita N., Hori H., Yamashita U.
  • Journal Title: Chemico-Bio Intera 177 Pages: 137-141
  • Peer Reviewed
• [Journal Article] Cucurbitacin D isolated from Trichosanthes kirilowii induces apoptosis in human hepatocellular carcinoma cells in vitro. (2009)
  • Author(s): Takahashi N., Yoshida Y., Sugiura T., Matsuno K., Fujino A, Yamashita U.
  • Journal Title: International Immunopharmacology 9 Pages: 508-513
  • Peer Reviewed
• [Journal Article] Formaldehyde inhalation activates signal transducer and activator of transcription 5 in immune cells. (2009)
  • Author(s): Yoshida Y., Ding N., Liu JQ., Noguchi J., Sugiura T., Kunugita N.
  • Journal Title: European Immunology Conference 39
  • Peer Reviewed
• [Journal Article] The NF-kappaB RelA subunit confers resistance to Leishmania major by inducing nitric oxide synthase 2 and Fas expression but not Th1 differentiation. (2009)
  • Author(s): Omata S., Kuroda E., Sugiura T., Yamashita U.
  • Journal Title: J Immunol 182 Pages: 4910-4916
  • Peer Reviewed
• [Journal Article] Effects of 1-bromopropane, a substitute for chlorofluorocarbons (2009)
  • Author(s): Yoshida Y., Nakano Y., Ueno S., Liu JQ., Fueta Y., Ishidao T., Kunugita N., Yanagihara N., Sugiura T., Yamashita U., Hori H.
  • Journal Title: on brain-derived neurotrophic factor (BDNF) expression Int ImmPharma 9 Pages: 433-438
  • Peer Reviewed
• [Journal Article] The indoor air pollutant 2-ethyl-hexanol activates CD4 cells. (2009)
  • Author(s): Yoshida, Y., 劉冀琴, 杉浦勉, 石田尾徹, 上野晋, 笛田由紀子, 欅田尚樹, 保利一, 山下優毅
  • Journal Title: Chemico-Bio Intera 177 Pages: 137-141
  • Peer Reviewed
• [Journal Article] Cucurbitacin D isolated from Trichosanthes kirilowii induces apoptosis in human hepatocellular carcinoma cells in vitro. (2009)
  • Author(s): Takahashi, N., Yoshida, Y., Sugiura, T., Masuno K., Fujino, A, Yamashita, U
  • Journal Title: International Immunopharmacology 9 Pages: 508-513
  • Peer Reviewed
• [Journal Article] Formaldehyde inhalation activates signal transducer and activator of transcription 5 in immune cells. (2009)
  • Author(s): Yoshida, Y., Ding, N., Liu, JQ., Noguchi, J., Sugiura, T., Kunugita, N.
  • Journal Title: European Immunology Conference 39
  • Peer Reviewed
• [Journal Article] The NF-kappaB RelA subunit confers resistance to Leishmania major by inducing nitric oxide synthase 2 and Fas expression but not Th1 differe ntiation. (2009)
  • Author(s): Omata, S., Kuroda, E., Sugiura, T., Yamashita, U.
  • Journal Title: J Immunol 182 Pages: 4910-4916
  • Peer Reviewed
• [Journal Article] Effects of 1-bromopropane, a substitute for chlorofluorocarbons, on brain-derived neurotrophic factor (BDNF) expression (2009)
  • Author(s): Yoshida, Y., Nakano, Y., Ueno, S., Liu, JQ., Fueta, Y., Ishidao, T., Kunugita, N., Yanagihara, N., Sugiura, T., Yamashita, U., Hori, H.
  • Journal Title: Int ImmPharma 9 Pages: 433-438
  • Peer Reviewed
• [Journal Article] Induction of prostaglandin E2 synthesis and microsomal prosta-glandin E synthase-1 expression in microglia by glioma-derived soluble factors. (2008)
  • Author(s): Nakano Y., Kuroda E., Kito T., Uematsu S., Akira S., Yokota A., Nishizawa S., Yamashita U.
  • Journal Title: J. Neurosurgery 108 Pages: 311-319
  • Peer Reviewed
• [Journal Article] Cutaneous hypersensitivities to hapten are controlled by IFN-gamma-upregulated keratinocyte Th1 chemokines and IFN-gamma-downregulated langerhans cell Th2 chemokines. (2008)
  • Author(s): Mori T, Kabashima K., Yoshiki R., Sugita K., Shiraishi N., Onoue A., Kuroda E., Kobayashi M., Yamashita U.
  • Journal Title: J.Invest.Dermatol. 128 Pages: 1719-1727
  • Peer Reviewed
• [Journal Article] Induction of prostaglandin E_2 synthesis and microsomal prosta-glandin E synthase-1 expression in microglia by glioma-derived soluble factors. (2008)
  • Author(s): Y. Nakano, et al.
  • Journal Title: J. Neurosurgery 108 Pages: 311-319
  • Peer Reviewed
• [Journal Article] Cutaneous hypersensitivities to hapten are controlled by IFN-gamma-upregulated keratinocyte Th1 chemokines and IFN-gamma-downregulated langerhans cell Th2 chemokines. (2008)
  • Author(s): T. Mori, et al.
  • Journal Title: J. Invest. Dermatol. 128 Pages: 1719-1727
  • Peer Reviewed
• [Journal Article] DNA-binding activity of NF-kB and phosphorylation of p65 are induced by N-acetylcysteine through phosphatidylinositol (PI) 3-kinase (2008)
  • Author(s): J. Q. Liu, et al.
  • Journal Title: Molecular Immunology 45 Pages: 3984-3989
  • Peer Reviewed
• [Presentation] BDNF produced by leukemia cells attenuates cytokine production in macrophages and induced Foxp3 positive cells through NF-AT, Smad and RhoA. (2010)
  • Author(s): Yoshida Y., Tsukada J.
  • Organizer: 14th International Congress of Immunology
  • Place of Presentation: Kobe, Japan
  • Year and Date: 2010-08-25
• [Presentation] Anti-proliferative activity of cucurbitacin D on T-cell leukemia through proteasome inhibition. (2010)
  • Author(s): Ding N. Yamashita U., Yoshida Y.
  • Organizer: 14th International Congress of Immunology
  • Place of Presentation: Kobe, Japan
  • Year and Date: 2010-08-25
• [Presentation] Oxidative stress and apoptotic changes in mouse macrophages exposed to cadmium. (2010)
  • Author(s): Sugiura T., 山下優毅
  • Organizer: 14th International Congress of Immunology
  • Place of Presentation: Kobe, Japan
  • Year and Date: 2010-08-25
• [Presentation] BDNF produced by leukemia cells attenuates cytokine production in macrophages and induced Foxp3 positive cells through NF-AT, Smad and RhoA. (2010)
  • Author(s): Yoshida, Y., Tsukada, J.
  • Organizer: 14th International Congress of Immunology
  • Place of Presentation: 神戸(神戸国際会議場)
  • Year and Date: 2010-08-25
• [Presentation] Anti-proliferative activity of cucurbitacin D on T-cell leukemia through proteasome inhibition. (2010)
  • Author(s): Ding, N.Yamashita, U., Yoshida, Y.
  • Organizer: 14th International Congress of Immunology
  • Place of Presentation: 神戸(神戸国際会議場)
  • Year and Date: 2010-08-25
• [Presentation] Oxidative stress and apoptotic changes in mouse macrophages exposed to cadmium. (2010)
  • Author(s): Sugiura, T., Yamashita, U.
  • Organizer: 14th International Congress of Immunology
  • Place of Presentation: 神戸(神戸国際会議場)
  • Year and Date: 2010-08-25
• [Presentation] Analysis of mechanism of the IL -1 induction by new proteasome inhibitor Cucurbitacin D. (2010)
  • Author(s): 吉田安宏
  • Organizer: Bit's 3rd. Annual World Cancer Congress 2010
  • Place of Presentation: Singapore
  • Year and Date: 2010-06-23
• [Presentation] Analysis of mechanism of the IL-1 induction by new proteasome inhibitor Cucurbitacin D (2010)
  • Author(s): Yoshida, Y.
  • Organizer: Bit's 3rd Annual World Cancer Congress 2010
  • Place of Presentation: シンガポール(シンガポールEXPO)
  • Year and Date: 2010-06-23
• [Presentation] BDNF produced by leukemia cells modulates immune responses. (2010)
  • Author(s): 吉田安宏
  • Organizer: 1st. World Congress of Immunodiseases and Therapy.
  • Place of Presentation: Beijing
  • Year and Date: 2010-05-16
• [Presentation] BDNF produced by leukemia cells modulates immune responses (2010)
  • Author(s): Yoshida, Y.
  • Organizer: 1st.World Congress of Immunodiseases and Therapy
  • Place of Presentation: 中国・北京(北京国際コンベンションセンター)
  • Year and Date: 2010-05-16
• [Presentation] Induction of apoptosis in T-cell leukemia by new drug which targeted a proteasome inhibition. (2009)
  • Author(s): Yoshida Y., Ding N., Yamashita U.
  • Organizer: World Congress of Gene-2009
  • Place of Presentation: 中国・佛山
  • Year and Date: 2009-12-06
• [Presentation] Induction of apoptosis in T-cell leukemia by new drug which targeted aproteasome inhibition. (2009)
  • Author(s): Yoshida, Y., Ding, N., Yamashita, U.
  • Organizer: World Congress of Gene-2009
  • Place of Presentation: 中国・佛山
  • Year and Date: 2009-12-06
• [Presentation] Cucurbitacin Dの転写および転写後修飾によるIL-1β産生の調節機構 (2009)
  • Author(s): 丁寧,吉田安宏,山下優毅
  • Organizer: 第39回日本免疫学会
  • Place of Presentation: 大阪
  • Year and Date: 2009-12-03
• [Presentation] BDNF produced by leukemia cells activates AP1 and NF-AT, which resulted in induction of Foxp3. (2009)
  • Author(s): 吉田安宏,丁寧,山下優毅
  • Organizer: 第39回日本免疫学会
  • Place of Presentation: 大阪
  • Year and Date: 2009-12-03
• [Presentation] カドミウムにより誘導される酸化傷害に対するレドックス制御におけるメタロチオネインの役割 (2009)
  • Author(s): 杉浦勉,山下優毅
  • Organizer: 第39回日本免疫学会
  • Place of Presentation: 大阪
  • Year and Date: 2009-12-03
• [Presentation] BDNF produced by leukemia cells activates AP1 and NF-AT, which resulted in induction of Foxp3. (2009)
  • Author(s): 吉田安宏, 丁〓, 山下優毅
  • Organizer: 第39回日本免疫学会総会・学術集会
  • Place of Presentation: 大阪(大阪国際会議場)
  • Year and Date: 2009-12-03
• [Presentation] カドミウムにより誘導される酸化傷害に対するレドックス制御におけるメタロチオネインの役割 (2009)
  • Author(s): 杉浦勉, 山下優毅
  • Organizer: 第39回日本免疫学会総会・学術集会
  • Place of Presentation: 大阪(大阪国際会議場)
  • Year and Date: 2009-12-03
• [Presentation] Cucurbitacin Dの転写および転写後修飾によるIL-1β産生の調節機構 (2009)
  • Author(s): Ding, N., 吉田安宏, 山下優毅
  • Organizer: 第39回日本免疫学会総会・学術集会
  • Place of Presentation: 大阪(大阪国際会議場)
  • Year and Date: 2009-12-02
• [Presentation] Triterpenoids cucurbitacin D isolated from cucurbitaceae induces apoptosis in adult T-cell leukemia through proteasome inhibition. 2009 (2009)
  • Author(s): Yoshida Y., Ding N., Yamashita U.
  • Organizer: 4th Medical Biotech Forum, International experts symposium
  • Place of Presentation: 大連
  • Year and Date: 2009-08-08
• [Presentation] Triterpenoids cucurbitacin D isolated from cucurbitaceae induces apoptosis in adult T-cell leukemia through proteasome inhibition. (2009)
  • Author(s): Yoshida, Y., Ding, N., Yamashita, U.
  • Organizer: 2009 4th Medical Biotech Forum, International experts symposium
  • Place of Presentation: 中国・大連
  • Year and Date: 2009-08-08
• [Presentation] プロスタグランジンD2による免疫反応の調節 (2008)
  • Author(s): 山下優毅,丁寧,吉田安宏
  • Organizer: 第26回産業医科大学学会総会
  • Place of Presentation: 北九州市
  • Year and Date: 2008-10-30
• [Presentation] プロスタグランジンD_2による免疫反応の調節 (2008)
  • Author(s): 山下優毅, 丁宇, 吉田安宏
  • Organizer: 第26回産業医科大学学会総会
  • Place of Presentation: 北九州市
  • Year and Date: 2008-10-30