1998 Fiscal Year Annual Research Report

胆汁酸の免疫調節作用に関する分子生物学的研究

Research Project

Project/Area Number	08457159
Research Institution	ASAHIKAWA MEDICAL COLLEGE
Principal Investigator	牧野勲旭川医科大学, 医学部, 副学長 (60088854)
Co-Investigator(Kenkyū-buntansha)	田中廣壽旭川医科大学, 医学部, 助教授 (00171794)
Keywords	胆汁酸 / 免疫系 / 転写因子 / 遺伝子発現 / 免疫学 / 分子生物学
Research Abstract	1) 主要組織適合抗原クラスI(MHC classI)遺伝子発現調節機構能の解析ヒト株化培養肝細胞において、 (i) 胆汁酸で活性化されるプロテインキナーゼCアイソフォームを推定した。 (ii) 胆汁酸によってMHC classI遺伝子プロモーターの誘導が起こることを明らかにした。現在、論文投稿準備中である。 2) ウルソデオキシコール酸の免疫調節作用機構の解明ウルソデオキシコール酸によるステロイドホルモン受容体の翻訳後修飾機構に関する研究が進展している。特に、green fluorescent proteinを用いた受容体の細胞内局在に関する実験系の整備が果たした役割が大きい。すでに、ウルソデオキシコール酸が作用する領域を特定し、転写共役因子と受容体との相互作用に関する解析も進展している。かかる成果は世界的にも画期的であり、今後のステロイドホルモン受容体を標的とした創薬に多大な影響を与える可能性がある。

Research Products
(31 results)

All Other

All Publications (31 results)

[Publications] I Makino & H Tanaka: "From a choleretic to an immunomodulator : Historical review of ursodeoxycholic acid as a medicament." J Gastroenterol Hepatol. 13. 659-664 (1998)
[Publications] 牧野勲: "ハインリッヒの法則" 内科. 80. 642-642 (1997)
[Publications] 牧野勲: "UDCAの免疫調節作用のメカニズム" 肝臓学の進歩. 23. 26-32 (1997)
[Publications] 牧野勲: "胆道感染症" 消化器疾患最新の治療. 97-98年. 364-366 (1997)
[Publications] 牧野勲: "胆石症(内科)" 1996今日の治療指針. 38. 409-410 (1996)
[Publications] 牧野勲、市原和夫: "胆石症" 治療. 78(増刊). 873-875 (1996)
[Publications] Kensaku Okamoto: "Redox regulation of nuclear import of the glucocorticoid receptor." J.Biol.Chem.274(印刷中). (1999)
[Publications] Yuichi Makino: "Direct association with thioredoxin allows redox regulation of the glucocorticoid receptor function." J.Biol.Chem.274・5. 3182-3188 (1999)
[Publications] Pekka J.Kallio: "Signal transduction in hypoxic cells : inducible nuclear translocation and recruitment of the CBP/p300 coactivator by the hypoxia-inducible factor-1α." EMBO J.17・22. 6573-6586 (1998)
[Publications] Fuminori Hirano: "Functional interference between Sp1 and NF-κB through the same DNA binding site." Mol.Cell.Biol.18. 1266-1274 (1998)
[Publications] Fuminori Hirano: "Alternative splice variants of IκBβ establish differential NF-κB signal responsiveness in human cells." Mol.Cell.Biol.18. 2596-2607 (1998)
[Publications] Masaki Hiramoto: "Nuclear-targeted suppression of NF-κB activity by the novel quinone derivative E3330" J.Immunol.160. 810-819 (1998)
[Publications] Kensaku Okamoto: "Restoration of the glucocorticoid receptor function by the phosphodiester compound of vitamin C and vitamin E,EPC-K1 via a redox-dependent mechanism." Biochem.Pharmacol.56・1. 79-86 (1998)
[Publications] Fuminori Hirano: "Inhibition of NF-κB-dependent transcription of human immunodeficiency virus 1 promoter by a phosphodiester compound of vitamin C and vitamin E,EPC-K1." Immunopharmacol.39・1. 31-38 (1998)
[Publications] 田中廣壽: "特集 : 核内レセプター研究の最前線「グルココルチコイドレセプターの機能」" 医学のあゆみ. 186・10. 689-693 (1998)
[Publications] 田中廣壽: "エタノールと肝細胞におけるATL-derived factor/Thioredoxin遺伝子発現" BIO Clinica. 13・11. 929-931 (1998)
[Publications] 田中廣壽: "グルココルチコイドレセプターの細胞内局在" 神経研究の進歩. 42・4. 558-565 (1998)
[Publications] 田中廣壽: "転写因子NF-κBによる遺伝子発現機構の解明と抗NF-κB薬開発に関する研究" 臨床薬理の進歩'98. (別刷). 119-121 (1998)
[Publications] Shin-ichi Hayashi: "Functional susceptibility of estrogen receptor by redox change with reference to a role of thioredoxin as a mediator." Nucleic Acids Res.25. 4035-4040 (1997)
[Publications] Takako Kawakami-Tani: "Effect of 1α-hydroxy vitamin D3 on serum levels of thyroid hormones in patients with untreated Graves'disease." Metabolism. 46. 1184-1188 (1997)
[Publications] 田中廣壽: "ステロイド作用の調節因子" 現代医療. 29・9. 2363-2369 (1997)
[Publications] 田中廣壽: "バセドウ病とビタミンD" 診断と治療. 85・7. 1168-1172 (1997)
[Publications] 田中廣壽: "MHCクラスII抗原遺伝子発現に及ぼすウルソデオキシコール酸(UDCA)の影響" 肝胆膵. 34・1. 37-40 (1997)
[Publications] 田中廣壽: "Green fluorescent protein(GFP)-グルココルチコイド受容体(GR)キメラ蛋白発現系を応用した免疫抑制薬のスクリーニング系の開発" 臨床薬理. 28・1. 389-340 (1997)
[Publications] Yuichi Makino: "Thioredoxin : a redox-regulating cellular cofactor for glucocorticoid hormone action." J.Clin.Invest.98. 2469-2477 (1996)
[Publications] Yuichi Makino: "Modulation of the glucocorticoid receptor function by metal ions." Mol.Pharmacol.49. 612-620 (1996)
[Publications] Hirotoshi Tanaka: "Ligand-independent activation of the glucocorticoid receptor by ursodeoxycholic acid." J.Immunol.156. 1601-1608 (1996)
[Publications] Fuminori Hirano: "Effects of ursodeoxycholic acid and chenodeoxycholic acid on major histocompatibility complex class I gene expression." J.Gastroenterol.31. 55-60 (1996)
[Publications] Fuminori Hirano: "Induction of the transcription factor AP-1 in cultured colon adenocarcinoma cells following exposure to bile acids." Carcinogenesis. 17. 427-433 (1996)
[Publications] 牧野勲: "肝臓病学 Basic Science,(戸田剛太郎ら編集)" 医学書院, 9 (1998)
[Publications] 牧野勲,中村公英: "食物線維-基礎と臨床(土井邦紘他編)" 朝倉書店, 15 (1997)

1998 Fiscal Year Annual Research Report

胆汁酸の免疫調節作用に関する分子生物学的研究

Principal Investigator

牧野 勲 旭川医科大学, 医学部, 副学長 (60088854)

Research Products

[Publications] I Makino & H Tanaka: "From a choleretic to an immunomodulator : Historical review of ursodeoxycholic acid as a medicament." J Gastroenterol Hepatol. 13. 659-664 (1998)

[Publications] 牧野 勲: "ハインリッヒの法則" 内科. 80. 642-642 (1997)

[Publications] 牧野 勲: "UDCAの免疫調節作用のメカニズム" 肝臓学の進歩. 23. 26-32 (1997)

[Publications] 牧野 勲: "胆道感染症" 消化器疾患最新の治療. 97-98年. 364-366 (1997)

[Publications] 牧野 勲: "胆石症(内科)" 1996今日の治療指針. 38. 409-410 (1996)

[Publications] 牧野 勲、市原和夫: "胆石症" 治療. 78(増刊). 873-875 (1996)

[Publications] Kensaku Okamoto: "Redox regulation of nuclear import of the glucocorticoid receptor." J.Biol.Chem.274(印刷中). (1999)

[Publications] Yuichi Makino: "Direct association with thioredoxin allows redox regulation of the glucocorticoid receptor function." J.Biol.Chem.274・5. 3182-3188 (1999)

[Publications] Pekka J.Kallio: "Signal transduction in hypoxic cells : inducible nuclear translocation and recruitment of the CBP/p300 coactivator by the hypoxia-inducible factor-1α." EMBO J.17・22. 6573-6586 (1998)

[Publications] Fuminori Hirano: "Functional interference between Sp1 and NF-κB through the same DNA binding site." Mol.Cell.Biol.18. 1266-1274 (1998)

[Publications] Fuminori Hirano: "Alternative splice variants of IκBβ establish differential NF-κB signal responsiveness in human cells." Mol.Cell.Biol.18. 2596-2607 (1998)

[Publications] Masaki Hiramoto: "Nuclear-targeted suppression of NF-κB activity by the novel quinone derivative E3330" J.Immunol.160. 810-819 (1998)

[Publications] Kensaku Okamoto: "Restoration of the glucocorticoid receptor function by the phosphodiester compound of vitamin C and vitamin E,EPC-K1 via a redox-dependent mechanism." Biochem.Pharmacol.56・1. 79-86 (1998)

[Publications] Fuminori Hirano: "Inhibition of NF-κB-dependent transcription of human immunodeficiency virus 1 promoter by a phosphodiester compound of vitamin C and vitamin E,EPC-K1." Immunopharmacol.39・1. 31-38 (1998)

[Publications] 田中廣壽: "特集 : 核内レセプター研究の最前線「グルココルチコイドレセプターの機能」" 医学のあゆみ. 186・10. 689-693 (1998)

[Publications] 田中廣壽: "エタノールと肝細胞におけるATL-derived factor/Thioredoxin遺伝子発現" BIO Clinica. 13・11. 929-931 (1998)

[Publications] 田中廣壽: "グルココルチコイドレセプターの細胞内局在" 神経研究の進歩. 42・4. 558-565 (1998)

[Publications] 田中廣壽: "転写因子NF-κBによる遺伝子発現機構の解明と抗NF-κB薬開発に関する研究" 臨床薬理の進歩'98. (別刷). 119-121 (1998)

[Publications] Shin-ichi Hayashi: "Functional susceptibility of estrogen receptor by redox change with reference to a role of thioredoxin as a mediator." Nucleic Acids Res.25. 4035-4040 (1997)

[Publications] Takako Kawakami-Tani: "Effect of 1α-hydroxy vitamin D3 on serum levels of thyroid hormones in patients with untreated Graves'disease." Metabolism. 46. 1184-1188 (1997)

[Publications] 田中廣壽: "ステロイド作用の調節因子" 現代医療. 29・9. 2363-2369 (1997)

[Publications] 田中廣壽: "バセドウ病とビタミンD" 診断と治療. 85・7. 1168-1172 (1997)

[Publications] 田中廣壽: "MHCクラスII抗原遺伝子発現に及ぼすウルソデオキシコール酸(UDCA)の影響" 肝胆膵. 34・1. 37-40 (1997)

[Publications] 田中廣壽: "Green fluorescent protein(GFP)-グルココルチコイド受容体(GR)キメラ蛋白発現系を応用した免疫抑制薬のスクリーニング系の開発" 臨床薬理. 28・1. 389-340 (1997)

[Publications] Yuichi Makino: "Thioredoxin : a redox-regulating cellular cofactor for glucocorticoid hormone action." J.Clin.Invest.98. 2469-2477 (1996)

[Publications] Yuichi Makino: "Modulation of the glucocorticoid receptor function by metal ions." Mol.Pharmacol.49. 612-620 (1996)

[Publications] Hirotoshi Tanaka: "Ligand-independent activation of the glucocorticoid receptor by ursodeoxycholic acid." J.Immunol.156. 1601-1608 (1996)

[Publications] Fuminori Hirano: "Effects of ursodeoxycholic acid and chenodeoxycholic acid on major histocompatibility complex class I gene expression." J.Gastroenterol.31. 55-60 (1996)

[Publications] Fuminori Hirano: "Induction of the transcription factor AP-1 in cultured colon adenocarcinoma cells following exposure to bile acids." Carcinogenesis. 17. 427-433 (1996)

[Publications] 牧野勲: "肝臓病学 Basic Science,(戸田剛太郎ら編集)" 医学書院, 9 (1998)

[Publications] 牧野 勲,中村公英: "食物線維-基礎と臨床(土井邦紘他編)" 朝倉書店, 15 (1997)

牧野勲旭川医科大学, 医学部, 副学長 (60088854)

[Publications] 牧野勲: "ハインリッヒの法則" 内科. 80. 642-642 (1997)

[Publications] 牧野勲: "UDCAの免疫調節作用のメカニズム" 肝臓学の進歩. 23. 26-32 (1997)

[Publications] 牧野勲: "胆道感染症" 消化器疾患最新の治療. 97-98年. 364-366 (1997)

[Publications] 牧野勲: "胆石症(内科)" 1996今日の治療指針. 38. 409-410 (1996)

[Publications] 牧野勲、市原和夫: "胆石症" 治療. 78(増刊). 873-875 (1996)

[Publications] 牧野勲,中村公英: "食物線維-基礎と臨床(土井邦紘他編)" 朝倉書店, 15 (1997)