The effect of exposure to chemical substance with bacterial toxin on the development of Th1/Th2 balance in infant mice.

• Project/Area Number: 19590612
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Hygiene
• Research Institution: National Institute for Environmental Studies
• Principal Investigator: YAMAMOTO Shoji National Institute for Environmental Studies, 環境リスク研究センター, 主任研究員 (40230552)
• Co-Investigator(Kenkyū-buntansha): FUJIMAKI Hidekazu 独立行政法人国立環境研究所, 環境リスク研究センター, 室長 (00124355) ; HIYOSHI Kyoko 静岡県立大学, 看護学部, 講師 (90405580) ; FUKUSHIMA Atsushi 独立行政法人国立環境研究所, 環境リスク研究センター, NIESポスドクフェロー (10442716)
• 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: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2008: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2007: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: 環境生理 / 小児健康影響 / アレルギー / 感染症 / 細菌 / 免疫学 / 有害化学物質

Research Abstract

The aims of the present study were to clarify whether the respiratory tract infection and stimulation can influence development of Th1 immune response and allergic reaction or not, and to investigate the effects of co-stimulation of the respiratory tract infectious agent with toluene which is one of the causative factors for chemical sensitivity and sick house syndrome can affect Th1/Th2 balance in infant mice using an allergic mouse model. Our findings indicate that (1) respiratory tract infection and stimulation with cell wall component of gram positive bacteria, peptidoglycan (PGN) does not affect development of Th1 immune response and allergic reaction in infant mice with ovalbumin (OVA) immunization ; (2) subcutaneous inoculation with BCG vaccine enhanced Th1 response via increased plasma IgG2a antibody and IFN-γexpression in lung and spleen of OVA immunized mice (this finding clearly shows that although BCG inoculation did not induce respiratory tract stimulation, it can be used for induction of Th1 response) ; (3) low level toluene exposure only from fetal to neonatal stage may enhance the systemic Th2 function in infant mice, however, the co-exposure of low level toluene with PGN shifted Th1/Th2 immunity to suppressive direction ; (4) in addition, the co-exposure of low level toluene with PGN in infant stage altered both Th1 and Th2 dependent blood Ig antibody level in 3 week-old mice.

Research Products

• [Journal Article] Up-regulation of neurotrophin-related gene expression in mouse hippocampus following low-level toluene exposure (2010)
  • Author(s): in-Shwe, T.T., Tsukahara, S., Yamamoto, S., Fukushima, A., Kunugita, N., Arashidani, K., Fujimaki, H.
  • Journal Title: Neuro. Toxicol. 31(1) Pages: 85-93
• [Journal Article] 揮発性有機化合物の胎仔期曝露による仔マウスのTh1, Th2型免疫応答のかく乱 (2010)
  • Author(s): 山元昭二・Tin-Tin-Win-Shwe・藤巻秀和
  • Journal Title: 岡山実験動物研究会報誌 26 Pages: 45-49
• [Journal Article] 揮発性有機化合物の胎仔期曝露による仔マウスのTh1, Th2型免疫応答のかく乱 (2010)
  • Author(s): 山元昭二・Tin-Tin Win-Shwe・藤巻秀和
  • Journal Title: 岡山実験動物研究会報誌 26 Pages: 45-49
• [Journal Article] The expression of nerve growth factor in mice lung following low-level toluene exposure (2009)
  • Author(s): Fujimaki, H., Win-Shwe, T.T., Yamamoto, S., Nakajima, D., Goto, S.
  • Journal Title: Toxicol. Lett. 191 Pages: 240-245
• [Journal Article] Suppression of Th1-and Th2-type immune responses in infant mouse spleen after prenatal and postnatal exposure to low-level toluene and peptidoglycan (2009)
  • Author(s): Yamamoto, S., Win-Shwe, T.T., Yoshida, Y., Kunugita, N., Arashidani, K., Fujimaki, H.
  • Journal Title: Inhal. Toxicol. 21(9) Pages: 793-802
• [Journal Article] Children's immunology, what can we learn from animal studies (2): Modulation of systemic Th1/Th2 immune response in infant mice after prenatal exposure to low-level toluene and toll-like receptor (TLR) 2 ligand (2009)
  • Author(s): Yamamoto, S., Win-Shwe, T.T., Yoshida, Y., Kunugita, N., Arashidani, K., Fujimaki, H.
  • Journal Title: J. Toxicol. Sci. 34
• [Journal Article] Modulation of systemic Th1/Th2 immune response in infant mice after prenatal exposure to low-level toluene and toll-like receptor(TLR)2 ligand (2009)
  • Author(s): Yamamoto, S., Win-Shwe, T.T., Yoshida, Y., Kunugita, N., Arashidani, K., Fujimaki, H.
  • Journal Title: J.Toxicol.Sci. 34 Pages: 341-348
  • NAID: 110007337702
  • Peer Reviewed
• [Journal Article] Suppression of Th1- and Th2- type immune responses in infant mouse spleen after prenatal and postnatal exposure to low-level toluene and peptidoglycan (2009)
  • Author(s): Yamamoto, S., Win-Shwe, T.T., Yoshida, Y., Kunugita, N., Arashidani, K., Fujimaki, H.
  • Journal Title: Inhal.Toxicol. 21 Pages: 793-802
  • Peer Reviewed
• [Journal Article] 時間的感受性要因に注目した化学物質の健康影響評価-マウス胎児期・授乳期における免疫・感染指標の検討- (2008)
  • Author(s): 山元昭二
  • Journal Title: 国立環境研究所特別研究報告書「環境リスク研究プログラム(中間報告) Pages: 18-19
• [Journal Article] Establishment of a Mouse Model to Asses Brain Neurotransmitter Level and Leaning Performance Simultaneously Following Toxic Chemical Exposure: Using in vivo Microdialysis and Schedule-Controlled Operant Behavior (2008)
  • Author(s): Win-Shwe, T.T., Hojo, R., Mitsushima, D., Nakajima, D., Yamamoto, S., Fujimaki, H.
  • Journal Title: J. UOEH. 31(1) Pages: 1-11
• [Journal Article] Strain Differences in Extracellular Amino Acid Neurotransmitter Levels in the Hippocampus of Major Histocompatibility Complex Congenic Mice in Response to Toluene Exposure (2008)
  • Author(s): Win-Shwe, T.T., Mitsushima, D., Yamamoto, S., Funabashi, T., Fujimaki, H.
  • Journal Title: Neuroimmunomodulation 16(3) Pages: 185-190
• [Journal Article] Role of CD4 (+) T cells in the modulation of neurotrophin production in mice exposed to low-level toluene (2008)
  • Author(s): Fujimaki, H., Win-Shwe, T.T., Yamamoto, S., Nakajima, D., Goto, S.
  • Journal Title: Immunopharmacol. Immunotoxicol. 31(1) Pages: 146-149
• [Journal Article] Role of CD4(+) T cells in the modulation of neurotrophin production in mice exposed to low-level toluene (2008)
  • Author(s): Fujimaki, H., Win Shwe, T. T., Yamamoto, S., Nakajima, D., Goto, S.
  • Journal Title: Immunopharmacol. Immunotoxicol. 31 Pages: 146-149
  • Peer Reviewed
• [Journal Article] Toluene induces rapid and reverse of hippocampal glutamate and taurine neurotransmitter levels in mice (2007)
  • Author(s): Win-Shwe, T.T., Mitsushima, D., Nakajima, D., Ahmed, S., Yamamoto, S., Tsukahara, S., Kakeyama, M., Goto, S., Fujimaki, H.
  • Journal Title: Toxicol. Lett. 168 Pages: 76-82
• [Journal Article] Effect of long-term exposure to low-level toluene on airway inflammatory response in mice (2007)
  • Author(s): Fujimaki, H., Yamamoto, S., Win-Shwe, T.T., Hojo, R., Sato, F., Kunugita, N., Arashidani, K.
  • Journal Title: Toxicol. Lett. 168 Pages: 132-139
• [Journal Article] Effects of low-level formaldehyde exposure on synaptic plasticity related gene expression in the hippocampus of immunized mice (2007)
  • Author(s): Ahmed, S., Tsukahara, S., Win-Shwe, T.T., Yamamoto, S., Kunugita, N., Arashidani, K., Fujimaki, H.
  • Journal Title: J. Neuroimmunol. 186 Pages: 104-111
• [Journal Article] Modulation of neurological related allergic reaction in mice exposed to low-level toluene (2007)
  • Author(s): Win Shwe, T.T., Yamamoto, S., Nakajima, D., Furuyama, A., Fukushima, A., Ahmed, S., Goto, S., Fujimaki, H.
  • Journal Title: Toxicol. Appl. Pharmacol. 222 Pages: 17-24
• [Journal Article] Athymic nude mice are insensitive to low-level toluene-induced up-regulation of memory-related gene expressions in the hippocampus (2007)
  • Author(s): Win-Shwe, T.T., Tsukahara, S., Ahmed, S., Fukushima, A., Yamamoto, S., Kakeyama, M., Nakajima, D., Goto, S., Kobayashi, T., Fujimaki, H.
  • Journal Title: Neurotoxicology 28 Pages: 957-964
• [Journal Article] Increased hippocampal mRNA expression of neuronal synaptic plasticity related genes in mice chronically exposed to toluene at a low-level human occupational-exposure (2007)
  • Author(s): Ahmed, S., Win-Shwe, T.T., Yamamoto, S., Tsukahara, S., Kunugita, N., Arashidani, K., Fujimaki, H.
  • Journal Title: Neurotoxicology 28 Pages: 168-174
• [Presentation] マウス胎仔期・新生仔期・乳仔期における低濃度トルエン曝露が免疫系の発達に及ぼす影響 (2009)
  • Author(s): 山元昭二, Tin-Tin-Win-Shwe, 欅田尚樹, 吉田安宏, 嵐谷奎一, 藤巻秀和
  • Organizer: 第16回日本免疫毒性学会学術大会
  • Place of Presentation: 旭川市民文化会館(北海道)
  • Year and Date: 2009-08-27
• [Presentation] A potential role of hippocampal memory function-related gene expression in developmental neurotoxicity of toluene (2009)
  • Author(s): Win-Shwe, T.T., Kunugita, N., Yamamoto, S., Arashidani, K., Fujimaki, H.
  • Organizer: 13th Congr. Eur. Fed. Neurol. Soc.
  • Place of Presentation: Florence
• [Presentation] Strain differences influence synaptic plasticity-related gene expression in olfactory bulb of a mouse model of allergy following toluene exposure (2009)
  • Author(s): Fujimaki, H., Win-Shwe T.T., Kunugita, N., Yamamoto, S., Arashidani, K.
  • Organizer: 13th Congr. Eur. Fed. Neurol. Soc.
  • Place of Presentation: Florence
• [Presentation] マウス胎仔期・新生仔期・乳仔期における低濃度トルエン曝露が免疫系の発達に及ぼす影響 (2009)
  • Author(s): 山元昭二・Tin-Tin-Win-Shwe・欅田尚樹・吉田安宏・嵐谷奎一・藤巻秀和
  • Organizer: 第16回日本免疫毒性学会学術大会
  • Place of Presentation: 旭川
• [Presentation] Effect of perinatal toluene exposure at different developmental phases on memory function-related gene expressions in mouse brain (2009)
  • Author(s): Tin-Tin-Win-Shwe, Kunugita, N., Yamamoto, S., Arashidani, K., Fujimaki, H.
  • Organizer: 50th Annu. Meet. Jpn. Soc. Atomos. Environ.
  • Place of Presentation: Yokohama
• [Presentation] マウス系統差で探るトルエン曝露に対する免疫系感受性要因 (2009)
  • Author(s): 欅田尚樹・Tin-Tin-Win-Shwe・山元昭二・吉田安宏・嵐谷奎一・藤巻秀和
  • Organizer: 第50回大気環境学会年会
  • Place of Presentation: 横浜
• [Presentation] Effects of toluene exposure on developmental immunotoxicity in infant mice brain (2009)
  • Author(s): Tin-Tin-Win-Shwe, Kunugita, N., Yamamoto, S., Arashidani, K., Fujimaki, H.
  • Organizer: 16th Annu. Meet. Jpn. Soc. Immunotoxicol.
  • Place of Presentation: Asahikawa
• [Presentation] アスベスト肺に対する常在細菌による急性曝露の影響 (2009)
  • Author(s): 日吉孝子・山元昭二・井上健一郎・市瀬孝道
  • Organizer: 第16回日本免疫毒性学会学術大会
  • Place of Presentation: 旭川
• [Presentation] トルエンの発達期影響-感染免疫- (2009)
  • Author(s): 山元昭二
  • Organizer: 第24回全国環境研究所交流シンポジウム「揮発性有機化合物(VOC)の動態と健康影響」
  • Place of Presentation: つくば
• [Presentation] VOCと免疫毒性 (2009)
  • Author(s): 欅田尚樹・吉田安宏・嵐谷奎一・Tin-Tin-Win-Shwe・山元昭二・藤巻秀和
  • Organizer: 第24回全国環境研究所交流シンポジウム「揮発性有機化合物(VOC)の動態と健康影響」
  • Place of Presentation: つくば
• [Presentation] Modulation of T cell development by biological and chemical agents neonatal mice (2008)
  • Author(s): Fujimaki, H., Win-Shwe, T.T., Yamamoto. S.
  • Organizer: 7th Annu. Eur. Life Sci. Org. Meet.
  • Place of Presentation: Nice
• [Presentation] トルエン曝露によるMHC-congenicマウス海馬における神経伝達物質レベルの変化 (2008)
  • Author(s): Tin-Tin-Win-Shwe・美津島大・山元昭二・藤巻秀和
  • Organizer: 第15回日本免疫毒性学会学術大会
  • Place of Presentation: 東京
• [Presentation] マウス乳児期におけるトルエン曝露とBCG刺激がTh1/Th2バランスの発達に及ぼす影響 (2008)
  • Author(s): 山元昭二・Tin-Tin Win-Shwe・藤巻秀和
  • Organizer: 第15回日本免疫毒性学会学術大会
  • Place of Presentation: 東京
• [Presentation] 低濃度トルエン曝露が発達期のマウス免疫系に及ぼす影響 (2008)
  • Author(s): 山元昭二・藤巻秀和
  • Organizer: 第35回日本トキシコロジー学会学術年会-こどもシンポジウム5-
  • Place of Presentation: 東京
• [Presentation] マウス胎生期および新生児期における低濃度トルエン曝露とペプチドグリカン刺激が全身性のTh1/Th2免疫バランスに及ぼす影響 (2007)
  • Author(s): 山元昭二・福島篤・Tin-Tin-Win-Shwe・北條理恵子・藤巻秀和
  • Organizer: 第14回日本免疫毒性学会学術大会
  • Place of Presentation: 神戸
• [Presentation] トルエン曝露によるマウス海馬における記憶関連遺伝子発現増強へのT細胞の役割 (2007)
  • Author(s): Tin-Tin-Win-Shwe・山元昭二・藤巻秀和
  • Organizer: 第14回日本免疫毒性学会学術大会
  • Place of Presentation: 神戸
• [Remarks]
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• [Remarks]
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