1999 年度実績報告書

ADF/チオレドキシンによる食品低アレルゲン化法の開発と食物アレルギー治療

研究課題

研究課題/領域番号	10357007
研究機関	福井医科大学
研究代表者	眞弓光文福井医科大学, 医学部, 教授 (70135581)
研究分担者	松尾雄志オリエンタル酵母工業(株), バイオ部, 部長淀井淳司京都大学, ウィルス研究所, 教授 (80108993) 片村憲司京都大学, 医学研究科, 講師 (40185806)
キーワード	食物アレルギー / 低アレルゲン化 / 治療 / 経口免疫寛容 / レドックス制御 / チオレドキシン / 卵アレルギー
研究概要	食物アレルギー患者のQOLの改善と治療法の開発を目的として、我々が遺伝子を同定したレドックス制御蛋白として細胞内外のレドックス環境の維持に深く関与しているADF/チオレドキシン(TRX)による食品低アレルゲン化と食物アレルギーの新しい治療法の可能性を検討し、以下の結果を得た。 (1)乳幼児期の食物アレルギーで最も頻度の高い卵アレルギーの主要アレルゲンであるオボムコイド(OM)およびオボアルブミン(OVA)は、チオレドキシン処理により消化酵素により分解されやすくなり、かつ、加熱処理に対して感受性が高まることにより、低アレルゲン化されることが明らかになった。TRX処理により低アレルゲン化された卵アレルゲンを経口摂取することにより、アレルギー反応を起こすことなく卵に対する経口免疫寛容が誘導され、卵アレルギーの早期治療法可能性が示唆された。 (2)上記の可能性を検討するために、OVAの経皮感作によるOVAアレルギーマウスモデルを作製し、このモデルではOVAの経口投与によりOVAに対する免疫寛容が誘導されることを明らかにした。この系を用いて、TRX処理OVAを経口投与することにより、TRX未処理のOVAと同様にOVAに対する免疫寛容が誘導できるかどうかの検討を準備した。 (3)TRXはケモカイン様の白血球遊走活性を認めることを明らかにすると同時に、マウスの実験において、TRXの静脈内投与のより循環血液中のTRX濃度を高くすると、LPS刺激などによる局所への白血球の血管外漏出を抑制することを明らかにし、TRXは生体内で免疫担当細胞の活性化や遊走を制御することを示唆した。以上の結果より、TRXは食物の低アレルゲン化に有用であるばかりではなく、食物アレルギー患者のアレルギー体質改善を目指した新しい治療法の開発に有用である可能性が示唆された。

研究成果

(37件)

すべてその他

すべて文献書誌 (37件)

[文献書誌] Ema, M., et al.: "Molecular mechanisms of transcription activation by HLF and HIF1alpha in response to hypoxia: their stabilization and redox signal-induced interaction with CBP/p300."EMBOJ.. 18. 1905-1914 (1999)
[文献書誌] Hashimoto, S., et al.: "Thioredoxin negatively regulates p38 MAP kinase activation and IL-6 production by tumor necrosis factor-alpha."Biochem. Biophys. Res. Commun.. 258. 443-447 (1999)
[文献書誌] Makino, Y., et al.: "Direct association with thioredoxin allows redox regulation of glucocorticoid receptor function."J. Biol. Chem.. 274. 3182-3188 (1999)
[文献書誌] Maruyama, T., et al.: "Activation of c-Src kinase is associated with in vitro decidualization of human endometrial stromal cells."Endocrinology. 140. 2632-2636 (1999)
[文献書誌] Maruyama, T., et al.: "Induction of thioredoxin, a redox-active protein, by ovarian steroid hormones during growth and differentiation of endometrial stromal cells in vitro."Endocrinology. 140. 365-372 (1999)
[文献書誌] Shimane, M., et al.: "Significant expression of G-CSF-induced gene-1 (GIG-1) protein in myeloid cells and NK cells."J. Leukoc. Biol.. 65. 109-116 (1999)
[文献書誌] Sugino, T., et al.: "Expression and distribution of redox regulatory protein, thioredoxin after metabolic impairment by 3-nitropropionic acid in rat brain."Neurosci. Lett.. 275. 145-148 (1999)
[文献書誌] Takagi, Y., et al.: "Proliferation of neuronal precursor cells in the dentate gyrus is accelerated after transient forebrain ischemia in mice."Brain Res.. 831. 283-287 (1999)
[文献書誌] Takagi, Y., et al.: "Localization of glutaredoxin (thioltransferase) in the rat brain and possible functional implications during focal ischemia."Biochem. Biophys. Res. Commun.. 258. 390-394 (1999)
[文献書誌] Takagi, Y., et al.: "Overexpression of thioredoxin in transgenic mice attenuates focal ischemic brain damage."Proc. Natl. Acad. Sci. U S A. 96. 4131-4136 (1999)
[文献書誌] Ueno, M., et al.: "Thioredoxin-dependent redox regulation of 53-mediated p21 activation."J. Biol. Chem.. 274. 35809-35815 (1999)
[文献書誌] Nishiyama, A., et al.: "Interaction of thioredoxin with p40phox, a phagocyte oxidase component, in yeast two-hybrid method."Immunol. Lett.. 68. 155-159 (1999)
[文献書誌] Bertini, R., et al.: "Thioredoxin, a redox enzyme released in infection and inflammation, is a unique chemoattractant for neutrophils, monocytes and T cells."J. Exp. Med.. 189. 1783-1789 (1999)
[文献書誌] Takashima, Y., et al.: "Differential expression of glutaredoxin and thioredoxin during monocytic differentiation."Immunol. Lett.. 68. 397-401 (1999)
[文献書誌] Nishiyama, A., et al.: "Identification of thioredoxin binding protein-2/vitamin D3 up-regulated protein 1 as a negative regulator of thioredoxin function and expression."J. Biol. Chem.. 274. 21645-21650 (1999)
[文献書誌] Nakamura, T., et al.: "Mouse glutaredoxin-cDNA cloning, high level expression in E. coli and its possible implication in redox regulation of the DNA binding activity in transcription factor PEPB2."Free Rad. Res.. 31. 357-365 (1999)
[文献書誌] Sasada, T., et al.: "Possible involvement of thioredoxin reductase as well as thioredoxin in cellular sensitivity to cis-Diamminedichloroplatinum (II)"Free Radic. Biol. Med.. 27. 504-514 (1999)
[文献書誌] Hirota, K., et al.: "Distict roles of thioredoxin in the cytoplasm and in the nucleus: a two step mechanism of redox regulation of transcription factor NF-kB"J. Biol. Chem.. 274. 27891-27897 (1999)
[文献書誌] Maurice, M., et al.: "Expression of the thioredoxin-thioredoxin reductase system in the inflamed joints of patients with rheumatoid arthritis."Arthritis Rheum.. 42. 2430-2439 (1999)
[文献書誌] Takahashi, T., et al.: "IgM anti-ganglioside antibodies induced by melanoma cell vaccine correlate with survival of melanoma patients."J. Invest. Dermatol.. 112. 205-209 (1999)
[文献書誌] Katamura, K., et al.: "Existence of activated CD4+ T cells in peripheral blood and their skin infiltration in ZAP-70 deficient SCID."Clin. Exp. Immunol.. 115. 124-130 (1999)
[文献書誌] Katamura, K.: "Differentiation of naive human CD4+ T cells. The role of prostaglandin E2."Allergol. Int.. 48. 7-14 (1999)
[文献書誌] Kiyomasu, T., et al.: "Hypomethylation of the proximal and intronic regulatory regions of the IFN-γ gene is not essential for its transcription by naive CD4+ T cells cultured with IL-4."Immunol. Lett.. 69. 239-245 (1999)
[文献書誌] Ueno, H., et al.: "Further characterization of memory T cells existing in a case of CD8 deficiency."Human Immunol.. 60. 1049-1053 (1999)
[文献書誌] Matsuda, S, et al.: "Temperature-sensitive ZAP-70 mutants degrading through a proteasome-independent pathway: restration of a kinase domein mutant by Cdc37."J. Biol. Chem.. 274. 34515-34518 (1999)
[文献書誌] Ueno, H., et al.: "ZAP-70 is required for calcium mobirization but is dispensable for MAPK superfamily activation in human T cells stimulated via CD2."Eur. J. Immunol.. 30. 78-86 (2000)
[文献書誌] Tsukahara, H., et al.: "Gas-phase oxidation of nitric oxide: chemical kinetics and rate constant."Nitric oxide: Biology and Chemistry. 3・3. 191-198 (1999)
[文献書誌] Tsukahara, H., et al.: "Early (4-7 days of age) dexamethasone therapy for prevention of chronic lung disease in preterm infants."Biol. Neonate. 76. 283-290 (1999)
[文献書誌] 眞弓光文: "リンパ球とアレルギー反応.特集小児のアレルギー疾患"小児内科. 31・3. 291-294 (1999)
[文献書誌] 眞弓光文: "卵アレルギー対策による難治型アトピー性皮膚炎発症予防の可能性.特集治り難いアトピー性皮膚炎"アレルギーの臨床. 19・5. 27-30 (1999)
[文献書誌] 眞弓光文: "小児アレルギーとヘルパーT細胞"日本小児アレルギー学会誌. 13・2. 1-6 (1999)
[文献書誌] 眞弓光文: "アトピー性皮膚炎.外来患者の素朴な疑問に応える -家庭でのケアとその指導Q&A-"小児科. 40・7. 906-914 (1999)
[文献書誌] 眞弓光文: "アトピー性皮膚炎と食物アレルギー乳幼児と成人の違い"アレルギー・免疫. 6・10. 44-48 (1999)
[文献書誌] 眞弓光文: "低アレルゲン化食品アトピー性皮膚炎の治療における最近の進歩"アレルギー科. 8・3. 181-185 (1999)
[文献書誌] 眞弓光文: "アレルギー.特集診断基準と治療の基本 -最近の進歩-"小児科臨床. 52・12. 2216-2224 (1999)
[文献書誌] 眞弓光文: "小児アトピー性皮膚炎の免疫学的機序.特集小児アトピー性皮膚炎"小児科診療. 63・1. 7-11 (2000)
[文献書誌] Masutani, H., et al.: "Role of thioredoxin family in the redox regulation of oxidative stress response and signalling. In Antioxidant and Redox regulation of genes. (分担執筆)"Edited by Chandan K. Sen, Helmut Sies and Patrick A. Baeurele, Academic press. 562(14) (1999)

1999 年度 実績報告書

ADF/チオレドキシンによる食品低アレルゲン化法の開発と食物アレルギー治療

研究代表者

眞弓 光文 福井医科大学, 医学部, 教授 (70135581)

研究成果

[文献書誌] Ema, M., et al.: "Molecular mechanisms of transcription activation by HLF and HIF1alpha in response to hypoxia: their stabilization and redox signal-induced interaction with CBP/p300."EMBOJ.. 18. 1905-1914 (1999)

[文献書誌] Hashimoto, S., et al.: "Thioredoxin negatively regulates p38 MAP kinase activation and IL-6 production by tumor necrosis factor-alpha."Biochem. Biophys. Res. Commun.. 258. 443-447 (1999)

[文献書誌] Makino, Y., et al.: "Direct association with thioredoxin allows redox regulation of glucocorticoid receptor function."J. Biol. Chem.. 274. 3182-3188 (1999)

[文献書誌] Maruyama, T., et al.: "Activation of c-Src kinase is associated with in vitro decidualization of human endometrial stromal cells."Endocrinology. 140. 2632-2636 (1999)

[文献書誌] Maruyama, T., et al.: "Induction of thioredoxin, a redox-active protein, by ovarian steroid hormones during growth and differentiation of endometrial stromal cells in vitro."Endocrinology. 140. 365-372 (1999)

[文献書誌] Shimane, M., et al.: "Significant expression of G-CSF-induced gene-1 (GIG-1) protein in myeloid cells and NK cells."J. Leukoc. Biol.. 65. 109-116 (1999)

[文献書誌] Sugino, T., et al.: "Expression and distribution of redox regulatory protein, thioredoxin after metabolic impairment by 3-nitropropionic acid in rat brain."Neurosci. Lett.. 275. 145-148 (1999)

[文献書誌] Takagi, Y., et al.: "Proliferation of neuronal precursor cells in the dentate gyrus is accelerated after transient forebrain ischemia in mice."Brain Res.. 831. 283-287 (1999)

[文献書誌] Takagi, Y., et al.: "Localization of glutaredoxin (thioltransferase) in the rat brain and possible functional implications during focal ischemia."Biochem. Biophys. Res. Commun.. 258. 390-394 (1999)

[文献書誌] Takagi, Y., et al.: "Overexpression of thioredoxin in transgenic mice attenuates focal ischemic brain damage."Proc. Natl. Acad. Sci. U S A. 96. 4131-4136 (1999)

[文献書誌] Ueno, M., et al.: "Thioredoxin-dependent redox regulation of 53-mediated p21 activation."J. Biol. Chem.. 274. 35809-35815 (1999)

[文献書誌] Nishiyama, A., et al.: "Interaction of thioredoxin with p40phox, a phagocyte oxidase component, in yeast two-hybrid method."Immunol. Lett.. 68. 155-159 (1999)

[文献書誌] Bertini, R., et al.: "Thioredoxin, a redox enzyme released in infection and inflammation, is a unique chemoattractant for neutrophils, monocytes and T cells."J. Exp. Med.. 189. 1783-1789 (1999)

[文献書誌] Takashima, Y., et al.: "Differential expression of glutaredoxin and thioredoxin during monocytic differentiation."Immunol. Lett.. 68. 397-401 (1999)

[文献書誌] Nishiyama, A., et al.: "Identification of thioredoxin binding protein-2/vitamin D3 up-regulated protein 1 as a negative regulator of thioredoxin function and expression."J. Biol. Chem.. 274. 21645-21650 (1999)

[文献書誌] Nakamura, T., et al.: "Mouse glutaredoxin-cDNA cloning, high level expression in E. coli and its possible implication in redox regulation of the DNA binding activity in transcription factor PEPB2."Free Rad. Res.. 31. 357-365 (1999)

[文献書誌] Sasada, T., et al.: "Possible involvement of thioredoxin reductase as well as thioredoxin in cellular sensitivity to cis-Diamminedichloroplatinum (II)"Free Radic. Biol. Med.. 27. 504-514 (1999)

[文献書誌] Hirota, K., et al.: "Distict roles of thioredoxin in the cytoplasm and in the nucleus: a two step mechanism of redox regulation of transcription factor NF-kB"J. Biol. Chem.. 274. 27891-27897 (1999)

[文献書誌] Maurice, M., et al.: "Expression of the thioredoxin-thioredoxin reductase system in the inflamed joints of patients with rheumatoid arthritis."Arthritis Rheum.. 42. 2430-2439 (1999)

[文献書誌] Takahashi, T., et al.: "IgM anti-ganglioside antibodies induced by melanoma cell vaccine correlate with survival of melanoma patients."J. Invest. Dermatol.. 112. 205-209 (1999)

[文献書誌] Katamura, K., et al.: "Existence of activated CD4+ T cells in peripheral blood and their skin infiltration in ZAP-70 deficient SCID."Clin. Exp. Immunol.. 115. 124-130 (1999)

[文献書誌] Katamura, K.: "Differentiation of naive human CD4+ T cells. The role of prostaglandin E2."Allergol. Int.. 48. 7-14 (1999)

[文献書誌] Kiyomasu, T., et al.: "Hypomethylation of the proximal and intronic regulatory regions of the IFN-γ gene is not essential for its transcription by naive CD4+ T cells cultured with IL-4."Immunol. Lett.. 69. 239-245 (1999)

[文献書誌] Ueno, H., et al.: "Further characterization of memory T cells existing in a case of CD8 deficiency."Human Immunol.. 60. 1049-1053 (1999)

[文献書誌] Matsuda, S, et al.: "Temperature-sensitive ZAP-70 mutants degrading through a proteasome-independent pathway: restration of a kinase domein mutant by Cdc37."J. Biol. Chem.. 274. 34515-34518 (1999)

[文献書誌] Ueno, H., et al.: "ZAP-70 is required for calcium mobirization but is dispensable for MAPK superfamily activation in human T cells stimulated via CD2."Eur. J. Immunol.. 30. 78-86 (2000)

[文献書誌] Tsukahara, H., et al.: "Gas-phase oxidation of nitric oxide: chemical kinetics and rate constant."Nitric oxide: Biology and Chemistry. 3・3. 191-198 (1999)

[文献書誌] Tsukahara, H., et al.: "Early (4-7 days of age) dexamethasone therapy for prevention of chronic lung disease in preterm infants."Biol. Neonate. 76. 283-290 (1999)

[文献書誌] 眞弓 光文: "リンパ球とアレルギー反応.特集 小児のアレルギー疾患"小児内科. 31・3. 291-294 (1999)

[文献書誌] 眞弓 光文: "卵アレルギー対策による難治型アトピー性皮膚炎発症予防の可能性.特集 治り難いアトピー性皮膚炎"アレルギーの臨床. 19・5. 27-30 (1999)

[文献書誌] 眞弓 光文: "小児アレルギーとヘルパーT細胞"日本小児アレルギー学会誌. 13・2. 1-6 (1999)

[文献書誌] 眞弓 光文: "アトピー性皮膚炎.外来患者の素朴な疑問に応える -家庭でのケアとその指導Q&A-"小児科. 40・7. 906-914 (1999)

[文献書誌] 眞弓 光文: "アトピー性皮膚炎と食物アレルギー 乳幼児と成人の違い"アレルギー・免疫. 6・10. 44-48 (1999)

[文献書誌] 眞弓 光文: "低アレルゲン化食品 アトピー性皮膚炎の治療における最近の進歩"アレルギー科. 8・3. 181-185 (1999)

[文献書誌] 眞弓 光文: "アレルギー.特集 診断基準と治療の基本 -最近の進歩-"小児科臨床. 52・12. 2216-2224 (1999)

[文献書誌] 眞弓 光文: "小児アトピー性皮膚炎の免疫学的機序.特集 小児アトピー性皮膚炎"小児科診療. 63・1. 7-11 (2000)

[文献書誌] Masutani, H., et al.: "Role of thioredoxin family in the redox regulation of oxidative stress response and signalling. In Antioxidant and Redox regulation of genes. (分担執筆)"Edited by Chandan K. Sen, Helmut Sies and Patrick A. Baeurele, Academic press. 562(14) (1999)

1999 年度実績報告書

眞弓光文福井医科大学, 医学部, 教授 (70135581)

[文献書誌] 眞弓光文: "リンパ球とアレルギー反応.特集小児のアレルギー疾患"小児内科. 31・3. 291-294 (1999)

[文献書誌] 眞弓光文: "卵アレルギー対策による難治型アトピー性皮膚炎発症予防の可能性.特集治り難いアトピー性皮膚炎"アレルギーの臨床. 19・5. 27-30 (1999)

[文献書誌] 眞弓光文: "小児アレルギーとヘルパーT細胞"日本小児アレルギー学会誌. 13・2. 1-6 (1999)

[文献書誌] 眞弓光文: "アトピー性皮膚炎.外来患者の素朴な疑問に応える -家庭でのケアとその指導Q&A-"小児科. 40・7. 906-914 (1999)

[文献書誌] 眞弓光文: "アトピー性皮膚炎と食物アレルギー乳幼児と成人の違い"アレルギー・免疫. 6・10. 44-48 (1999)

[文献書誌] 眞弓光文: "低アレルゲン化食品アトピー性皮膚炎の治療における最近の進歩"アレルギー科. 8・3. 181-185 (1999)

[文献書誌] 眞弓光文: "アレルギー.特集診断基準と治療の基本 -最近の進歩-"小児科臨床. 52・12. 2216-2224 (1999)

[文献書誌] 眞弓光文: "小児アトピー性皮膚炎の免疫学的機序.特集小児アトピー性皮膚炎"小児科診療. 63・1. 7-11 (2000)