1998 Fiscal Year Annual Research Report

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

Research Project

Project/Area Number	10357007
Research Category	Grant-in-Aid for Scientific Research (A)
Research Institution	福井医科大学
Principal Investigator	眞弓光文福井医科大学, 医学部, 教授 (70135581)
Co-Investigator(Kenkyū-buntansha)	松尾雄志オリエンタル酵母工業, バイオ部, 部長淀井淳司京都大学, ウイルス研究所, 教授 (80108993) 片村憲司京都大学, 医学研究科, 助手 (40185806)
Keywords	食物アレルギー / 卵アレルギー / 低アレルゲン化 / チオレドキシン / 免疫寛容
Research Abstract	乳幼児期に多く見られる食物アレルギーは有効な治療法に乏しく、患者は原因食物を除去せざるを得ず、低アレルゲン化食品の開発は極めて重要である。また、低アレルゲン化食物抗原により患者に免疫寛容を誘導して食物アレルギーを治療しうる可能性が示唆される。小児期の食物アレルギーとして最も頻度の高い卵アレルギーでは、患者全員にオボアルブミン(OA)に対する、また75%にオボムコイド(OM)に対するIgEが存在した。我々がATL由来因子(ADF)としてクローニングしたヒトチオレドキシン(TRX)は分子量12kDの酸化還元酵素で、その活性部位にあるふたつのシステイン基の間でジスルフィド結合を作る酸化型は、NADPHとNADPH-TRX reductaseによりジチオールの還元型となり、標的蛋白のジスルフィド結合を還元する。OAやOMのアレルゲン性の維持には分子内のジスルフィド結合が重要な役割を果たしていることから、TRXの還元作用を利用してOAおよびOMの分子内ジスルフィド結合を還元することにより、抗原性が低下するかどうかを検討した。まず、遺伝子工学的手法を用いて、ヒトTRXと酵母TRXの大量生産を可能にした。このリコンビナントTRXを用いて試験管内でOAとOMを処理すると、消化酵素であるペプシンやトリプシンで容易に消化された。さらに、チオレドキシンと消化酵素で処理されたOAとOMは特異IgEとの結合性が著しく低下し、低アレルゲン化されたことが示された。低アレルゲン化抗原によりヘルパーT細胞のサイトカイン産生が変化するかどうか、体内の抗原提示細胞内においてもTRXにより抗原分子の還元処理が行われるかどうかの検討が今後の課題である。

Research Products

(25 results)

All Other

All Publications (25 results)

[Publications] 眞弓光文: "アレルギーとT細胞・サイトカイン" 小児科診療特大号小児アレルギーのすべて. 61・4. 518-521 (1998)
[Publications] 眞弓光文: "免疫学からみたアトピー性皮膚炎" 日本小児科学会雑誌. 10. 749-752 (1998)
[Publications] 眞弓光文: "卵アレルギー患者に対する予防接種について" infoAllergy. 6. 7-7 (1998)
[Publications] 眞弓光文: "食物低アレルゲン化の新しい戦略" 最新医学. 53・12. 99-103 (1998)
[Publications] M.Mayumi他: "Development of antigen-specific IgE antibodies in atopic and non-atopic infannts : Diagnostic value of low levels of IgE against egg white in infants atopic dermatitis." Allergology International. 47. 129-136 (1998)
[Publications] H.Tsukahara他: "Urinary excretion of aquaporin-2in term and preterm infants." Early Human Development. 51. 31-37 (1998)
[Publications] H.Tsukahara他: "Renal water channel expression in newborn infants : measurement of urinary excretion of aquaporin-2." Metabolism. 47. 1344-1347 (1998)
[Publications] H.Tsukahara他: "Endothelin subtype A receptor antagonist induces osteopenia in growing rats." Metabolism. 47. 1403-1407 (1998)
[Publications] K.Katamura他: "IL-4 and Prostaglandin E2 inhibit hypometylation of the 5'regulatory region of IFN-γ gene during differentiation oa naive CD4_+ Tcells." Molecular Immunology. 35. 39-45 (1998)
[Publications] K.Katamura: "Differentiation of naive human CD4_+ T cells into Th2 cells. The role of prostaglandin E2." Allergology International. 印刷中.
[Publications] K.Katamura他: "Existence of activated and memory CD4^+ T cells in peripheral blood and their skin infiltration in CD8 deficiency." Clinical and Experimental Immunology. 115. 124-130 (1999)
[Publications] Y.Takagi他: "Redox control of neuronal damage during brain ischemia after middle cerebral artery occlusion in the rat : Immunohistochemical and hybridization studies of thioredoxin." Journal of Cerebral Blood Flow and Metabolism. 18. 206-214 (1998)
[Publications] Y.Takagi他: "Expression of thioredoxin is enhanced in atherosclerotic plaques and during neointima formation in rat arteries." Laboratory Investigation. 78. 957-966 (1998)
[Publications] M.Asahina他: "Expression of adult T cell leukemia-derived factor in human brain and peripheral nerve tissues." Dementia and Geriatric Cognitive Disorders. 9. 181-185 (1998)
[Publications] Y.Takagi他: "Expression and distribution of redox regulatory protein, thioredoxin during transient focal brain ischemia in the rat." Neuroscience Letters. 251. 25-28 (1998)
[Publications] H.Shibuki他: "Protective effect of adult T-cell leukemia-derived factor on retinal ischemia-reperfusion injury in the rat." Investigative Ophthalmology and Visual Science. 39. 1470-1477 (1998)
[Publications] M.Hotta他: "Pancreatic beta-cell-specific expression of thioredoxin, an anti-oxidative and anti-apoptotic protein, prevents autoimmune diabetes as well as streptozotocin-induced diabets" Journal of Exprimental Medicine. 188. 1445-1451 (1998)
[Publications] K.Mansur他: "Up-regulation of thioredoxin expression in motor neurons after nerve injury." Molecular Brain Research. 62. 86-91 (1998)
[Publications] S.Ueda他: "Redox regulation of caspase-3(like) protease activity : regulatory roles of thioredoxin and cytochromec." Jounal of Immunology. 161. 6689-6695 (1998)
[Publications] H.Nakamura他: "Redox regulation by thioredoxin in host defense." Current Trends in Immunology. 1. 133-140 (1998)
[Publications] T.Maruyama他: "Induction of thioredoxin, a redox-active protein, by ovarian steroidhormones during growth and differentiation of endometrial stromal cells in vitro." Endocrinology. 140. 365-372 (1999)
[Publications] 眞弓光文: "アレルギー疾患(喘息、アトピー性皮膚炎)の病態喘息やアトピー性皮膚炎はどのように発病するか. 小児喘息・アレルギー疾患の予防と治療に役立つ栄養・食生活鳥居新平編." 医学書院, 234 (1998)
[Publications] T.Ohno他(分担執筆): "Thioredox in and its involvement in the redox regulation of transcription factors, NF-kBand AP-1. In “Oxygen Homeostasis and Its Dynamics" edited by Y.Ishimura, H.Shimada, M.Suematsu." Springer-Verlag Tokyo, 620 (1998)
[Publications] A.Nishiyama他(分担執筆): "Detection of a Nuclear 60-kDa protein coimmunoprecipitated with human thioredoxin. In “Oxygen Homeostasis and Its Dynamics" edited by Y.Ishimura, H.Shimada, M.Suematsu." Springer-Verlag Tokyo, 620 (1998)
[Publications] H.Kato他(分担執筆): "Diagnosis of Epstein-Barrvirus lymphoma after liver transplantation. In “Epstein-Barrvirus and Human Cancer" edited by T.Osato, K.Takada, M.Tokunaga. Gann Monograph in Cancer Research" 学術出版センター(東京), 220 (1998)

1998 Fiscal Year Annual Research Report

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

Principal Investigator

眞弓 光文 福井医科大学, 医学部, 教授 (70135581)

Research Products

[Publications] 眞弓光文: "アレルギーとT細胞・サイトカイン" 小児科診療 特大号小児アレルギーのすべて. 61・4. 518-521 (1998)

[Publications] 眞弓光文: "免疫学からみたアトピー性皮膚炎" 日本小児科学会雑誌. 10. 749-752 (1998)

[Publications] 眞弓光文: "卵アレルギー患者に対する予防接種について" infoAllergy. 6. 7-7 (1998)

[Publications] 眞弓光文: "食物低アレルゲン化の新しい戦略" 最新医学. 53・12. 99-103 (1998)

[Publications] M.Mayumi他: "Development of antigen-specific IgE antibodies in atopic and non-atopic infannts : Diagnostic value of low levels of IgE against egg white in infants atopic dermatitis." Allergology International. 47. 129-136 (1998)

[Publications] H.Tsukahara他: "Urinary excretion of aquaporin-2in term and preterm infants." Early Human Development. 51. 31-37 (1998)

[Publications] H.Tsukahara他: "Renal water channel expression in newborn infants : measurement of urinary excretion of aquaporin-2." Metabolism. 47. 1344-1347 (1998)

[Publications] H.Tsukahara他: "Endothelin subtype A receptor antagonist induces osteopenia in growing rats." Metabolism. 47. 1403-1407 (1998)

[Publications] K.Katamura他: "IL-4 and Prostaglandin E2 inhibit hypometylation of the 5'regulatory region of IFN-γ gene during differentiation oa naive CD4_+ Tcells." Molecular Immunology. 35. 39-45 (1998)

[Publications] K.Katamura: "Differentiation of naive human CD4_+ T cells into Th2 cells. The role of prostaglandin E2." Allergology International. 印刷中.

[Publications] K.Katamura他: "Existence of activated and memory CD4^+ T cells in peripheral blood and their skin infiltration in CD8 deficiency." Clinical and Experimental Immunology. 115. 124-130 (1999)

[Publications] Y.Takagi他: "Redox control of neuronal damage during brain ischemia after middle cerebral artery occlusion in the rat : Immunohistochemical and hybridization studies of thioredoxin." Journal of Cerebral Blood Flow and Metabolism. 18. 206-214 (1998)

[Publications] Y.Takagi他: "Expression of thioredoxin is enhanced in atherosclerotic plaques and during neointima formation in rat arteries." Laboratory Investigation. 78. 957-966 (1998)

[Publications] M.Asahina他: "Expression of adult T cell leukemia-derived factor in human brain and peripheral nerve tissues." Dementia and Geriatric Cognitive Disorders. 9. 181-185 (1998)

[Publications] Y.Takagi他: "Expression and distribution of redox regulatory protein, thioredoxin during transient focal brain ischemia in the rat." Neuroscience Letters. 251. 25-28 (1998)

[Publications] H.Shibuki他: "Protective effect of adult T-cell leukemia-derived factor on retinal ischemia-reperfusion injury in the rat." Investigative Ophthalmology and Visual Science. 39. 1470-1477 (1998)

[Publications] M.Hotta他: "Pancreatic beta-cell-specific expression of thioredoxin, an anti-oxidative and anti-apoptotic protein, prevents autoimmune diabetes as well as streptozotocin-induced diabets" Journal of Exprimental Medicine. 188. 1445-1451 (1998)

[Publications] K.Mansur他: "Up-regulation of thioredoxin expression in motor neurons after nerve injury." Molecular Brain Research. 62. 86-91 (1998)

[Publications] S.Ueda他: "Redox regulation of caspase-3(like) protease activity : regulatory roles of thioredoxin and cytochromec." Jounal of Immunology. 161. 6689-6695 (1998)

[Publications] H.Nakamura他: "Redox regulation by thioredoxin in host defense." Current Trends in Immunology. 1. 133-140 (1998)

[Publications] T.Maruyama他: "Induction of thioredoxin, a redox-active protein, by ovarian steroidhormones during growth and differentiation of endometrial stromal cells in vitro." Endocrinology. 140. 365-372 (1999)

[Publications] 眞弓光文: "アレルギー疾患(喘息、アトピー性皮膚炎)の病態 喘息やアトピー性皮膚炎はどのように発病するか. 小児喘息・アレルギー疾患の予防と治療に役立つ栄養・食生活 鳥居新平編." 医学書院, 234 (1998)

[Publications] T.Ohno他(分担執筆): "Thioredox in and its involvement in the redox regulation of transcription factors, NF-kBand AP-1. In “Oxygen Homeostasis and Its Dynamics" edited by Y.Ishimura, H.Shimada, M.Suematsu." Springer-Verlag Tokyo, 620 (1998)

[Publications] A.Nishiyama他(分担執筆): "Detection of a Nuclear 60-kDa protein coimmunoprecipitated with human thioredoxin. In “Oxygen Homeostasis and Its Dynamics" edited by Y.Ishimura, H.Shimada, M.Suematsu." Springer-Verlag Tokyo, 620 (1998)

[Publications] H.Kato他(分担執筆): "Diagnosis of Epstein-Barrvirus lymphoma after liver transplantation. In “Epstein-Barrvirus and Human Cancer" edited by T.Osato, K.Takada, M.Tokunaga. Gann Monograph in Cancer Research" 学術出版センター(東京), 220 (1998)

眞弓光文福井医科大学, 医学部, 教授 (70135581)

[Publications] 眞弓光文: "アレルギーとT細胞・サイトカイン" 小児科診療特大号小児アレルギーのすべて. 61・4. 518-521 (1998)

[Publications] 眞弓光文: "アレルギー疾患(喘息、アトピー性皮膚炎)の病態喘息やアトピー性皮膚炎はどのように発病するか. 小児喘息・アレルギー疾患の予防と治療に役立つ栄養・食生活鳥居新平編." 医学書院, 234 (1998)