炎症性疾患におけるHeme oxygenase-1 (HO-1) の発現
はじめに 酸化ストレスは動脈硬化, 神経変性疾患, 炎症性疾患などの病態に関与する因子として注日されている1). 生体内では常に酸化ストレスが発生しており, 一方ではその影響を回避するシステムを備え, 恒常性の維持に努めている. Heme oxygenase-1(HO-1)は抗酸化・炎症作用など,細胞保護作用“cytoprotection"と総称される様々な生理活性を有し, 生体の恒常性維持の一翼を担っている. 実際, 多様な呼吸器疾患, 炎症疾患, 神経疾患の実験動物モデルにおいて, HO-1遺伝子導入療法や誘導療法の有効性が示されている1). また, ヒトの諸疾患におけるHO-1...
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| Published in | 炎症・再生 Vol. 25; no. 5; pp. 431 - 435 |
|---|---|
| Main Authors | , , , |
| Format | Journal Article |
| Language | Japanese |
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一般社団法人 日本炎症・再生医学会
2005
日本炎症・再生医学会 |
| Online Access | Get full text |
| ISSN | 1346-8022 1880-5795 |
| DOI | 10.2492/jsir.25.431 |
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| Abstract | はじめに 酸化ストレスは動脈硬化, 神経変性疾患, 炎症性疾患などの病態に関与する因子として注日されている1). 生体内では常に酸化ストレスが発生しており, 一方ではその影響を回避するシステムを備え, 恒常性の維持に努めている. Heme oxygenase-1(HO-1)は抗酸化・炎症作用など,細胞保護作用“cytoprotection"と総称される様々な生理活性を有し, 生体の恒常性維持の一翼を担っている. 実際, 多様な呼吸器疾患, 炎症疾患, 神経疾患の実験動物モデルにおいて, HO-1遺伝子導入療法や誘導療法の有効性が示されている1). また, ヒトの諸疾患におけるHO-1の役割についても情報が蓄積されつつある. 本稿では最近の知見を踏まえ, 私どもの研究結果を交えながら, 特に炎症性疾患におけるHO-1発現制御を中心に概説する. Heme oxygenase-1(HO-1) HO-1はheatshock protein（HSP)-32とも呼ばれる32kDのヘム分解酵素である1). |
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| AbstractList | はじめに 酸化ストレスは動脈硬化, 神経変性疾患, 炎症性疾患などの病態に関与する因子として注日されている1). 生体内では常に酸化ストレスが発生しており, 一方ではその影響を回避するシステムを備え, 恒常性の維持に努めている. Heme oxygenase-1(HO-1)は抗酸化・炎症作用など,細胞保護作用“cytoprotection"と総称される様々な生理活性を有し, 生体の恒常性維持の一翼を担っている. 実際, 多様な呼吸器疾患, 炎症疾患, 神経疾患の実験動物モデルにおいて, HO-1遺伝子導入療法や誘導療法の有効性が示されている1). また, ヒトの諸疾患におけるHO-1の役割についても情報が蓄積されつつある. 本稿では最近の知見を踏まえ, 私どもの研究結果を交えながら, 特に炎症性疾患におけるHO-1発現制御を中心に概説する. Heme oxygenase-1(HO-1) HO-1はheatshock protein（HSP)-32とも呼ばれる32kDのヘム分解酵素である1). |
| Author | 小林, 秀郎 石ヶ坪, 良明 岳野, 光洋 桐野, 洋平 |
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| References | 14) Makino N, Suematsu M, Sugiura Y, Morikawa H, Shiomi S, Goda N, Sana T, Nimura Y, Sugimachi K, Ishimura Y: Altered expression of heme oxygenase-1 in the livers of patients with portal hypertensive diseases. Hepatology, 33: 32-42, 2001. 23) Kataoka K, Handa H, Nishizawa M: Induction of cellular antioxidative stress genes through heterodimeric transcription factor Nrf2/small Maf by antirheumatic gold (I) compounds. J Biol Chem, 276: 34074-34081, 2001. 7) Inoue S, Suzuki M, Nagashima Y, Suzuki S, Hashiba T, Tsuburai T, Ikehara K, Matsuse T, Ishigatsubo Y: Transfer of heme oxygenase 1 cDNA by a replication-deficient adenovirus enhances interleukin 10 production from alveolar macrophages that attenuates lipopolysaccharide-induced acute lung injury in mice. Hum Gene Ther, 12: 967-979, 2001. 12) Poss KD, Tonegawa S: Reduced stress defense in heme oxygenase 1-deficient cells. Proc Natl Acad Sci USA, 94: 10925-10930, 1997. 21) Dong Z, Lavrovsky Y, Venkatachalam MA, Roy AK: Heme oxygenase-1 in tissue pathology: the Yin and Yang. Am J Pathol, 156: 1485-1488, 2000. 10) Tsuburai T, Kaneko T, Nagashima Y, Ueda A, Tagawa A, Shinohara T, Ishigatsubo Y: Pseudomonas aeruginosa-induced neutrophilic lung inflammation is attenuated by adenovirus-mediated transfer of the heme oxygenase 1 cDNA in mice. Hum Gene Ther, 15: 273-285, 2004. 22) Maruhashi K, Kasahara Y, Ohta K, Wada T, Ohta K, Nakamura N, Toma T, Koizumi S, Yachie A: Paradoxical enhancement of oxidative cell injury by overexpression of heme oxygenase-1 in an anchorage-dependent cell ECV304. J Cell Biochem, 93: 552-562, 2004. 25) 吉川敏一, 内藤裕二 : 炎症と活性酸素, 一酸化窒素 (NO), 一酸化炭素 (CO)―炎症性腸疾患を中心に―. 炎症・再生, 24(5): 545-552, 2004. 11) Takeda Y, Takeno M, Iwasaki M, Kobayashi H, Kirino Y, Ueda A, Nagahama K, Aoki I, Ishigatsubo Y: Chemical induction of HO-1 suppresses lupus nephritis by reducing local iNOS expression and synthesis of anti-dsDNA anti-body. Clin Exp Immunol, 138: 237-244, 2004. 6) Harrison PM, Arosio P: The ferritins: molecular properties, iron storage function and cellular regulation. Biochim Biophys Acta, 1275: 161-203, 1996. 24) Lee TS, Chang CC, Zhu Y, Shyy JY: Simvastatin induces heme oxygenase-1: a novel mechanism of vessel protection. Circulation, 110: 1296-1302, 2004. 13) Yachie A, Niida Y, Wada T, Igarashi N, Kaneda H, Toma T, Ohta K, Kasahara Y, Koizumi S: Oxidative stress causes enhanced endothelial cell injury in human heme oxygenase-1 deficiency. J Clin Invest, 103: 129-135, 1999. 19) Kirino Y, Takeno M, Iwasaki M, Ueda A, Ohno S, Shirai A, Kanamori H, Tanaka K, Ishigatsubo Y: Increased serum HO-1 in hemophagocytic syndrome and adult-onset Still's disease: Use in the differential diagnosis of hyperterritinemia. Arthritis Res Ther, 7: R616-R624, 2005. 1) Morse D, Choi AM: Heme oxygenase-1: the “emerging molecule” has arrived. Am J Respir Cell Mol Biol, 27: 8-16, 2002. 9) Tsuburai T, Suzuki M, Nagashima Y, Suzuki S, Inoue S, Hasiba T, Ueda A, Ikehara K, Matsuse T, Ishigatsubo Y: Adenovirus-mediated transfer and overexpression of heme oxygenase 1 cDNA in lung prevents bleomycin-induced pulmonary fibrosis via a Fas-Fas ligand-independent pathway. Hum Gene Ther, 13: 1945-1960, 2002. 2) Sun J, Brand M, Zenke Y, Tashiro S, Groudine M, Igarashi K: Heme regulates the dynamic exchange of Bach1 and NF-E2-related factors in the Maf transcription factor network. Proc Natl Acad Sci USA, 101: 1461-1466, 2004. 16) Schipper HM, Chertkow H, Mehindate K, Frankel D, Melmed C, Bergman H: Evaluation of heme oxygenase-1 as a systemic biological marker of sporadic AD. Neurology, 54: 1297-1304, 2000. 15) Mayerhofer M, Florian S, Krauth MT, Aichberger KJ, Bilban M, Marculescu R, Printz D, Fritsch G, Wagner O, Selzer E, Sperr WR, Valent P, Sillaber C: Identification of heme oxygenase-1 as a novel BCR/ABL-dependent survival factor in chronic myeloid leukemia. Cancer Res, 64: 3148-3154, 2004. 8) Hashiba T, Suzuki M, Nagashima Y, Suzuki S, Inoue S, Tsuburai T, Matsuse T, Ishigatubo Y: Adenovirus-mediated transfer of heme oxygenase-1 cDNA attenuates severe lung injury induced by the influenza virus in mice. Gene Ther, 8: 1499-1507, 2001. 20) Suttner DM, Dennery PA: Reversal of HO-1 related cytoprotection with increased expression is due to reactive iron. FASEB J, 13: 1800-1809, 1999. 4) Suematsu M, Goda N, Sano T, Kashiwagi S, Egawa T, Shinoda Y, Ishimura Y: Carbon monoxide: an endogenous modulator of sinusoidal tone in the perfused rat liver. J Clin Invest, 96: 2431-2437, 1995. 18) Yachie A, Toma T, Mizuno K, Okamoto H, Shimura S, Ohta K, Kasahara Y, Koizumi S: Heme oxygenase-1 production by peripheral blood monocytes during acute inflammatory illnesses of children. Exp Biol Med, 228: 550-556, 2003. 3) Morita T, Perrella MA, Lee ME, Kourembanas S: Smooth muscle cell-derived carbon monoxide is a regulator of vascular cGMP. Proc Natl Acad Sci USA, 92: 1475-1479, 1995. 17) Lee TS, Tsai HL, Chau LY: Induction of heme oxygenase-1 expression in murine macrophages is essential for the anti-inflammatory effect of low dose 15-deoxy-Delta12,14-prostaglandin J2. J Biol Chem, 278: 19325-19330, 2003. 5) Hayashi S, Takamiya R, Yamaguchi T, Matsumoto K, Tojo SJ, Tamatani T, Kitajima M, Makino N, Ishimura Y, Suematsu M: Inducation of heme oxygenase-1 suppresses venular leukocyte adhesion elicited by oxidative stress: role of bilirubin generated by the enzyme. Circ Res, 85: 663-671, 1999. |
| References_xml | – reference: 22) Maruhashi K, Kasahara Y, Ohta K, Wada T, Ohta K, Nakamura N, Toma T, Koizumi S, Yachie A: Paradoxical enhancement of oxidative cell injury by overexpression of heme oxygenase-1 in an anchorage-dependent cell ECV304. J Cell Biochem, 93: 552-562, 2004. – reference: 12) Poss KD, Tonegawa S: Reduced stress defense in heme oxygenase 1-deficient cells. Proc Natl Acad Sci USA, 94: 10925-10930, 1997. – reference: 5) Hayashi S, Takamiya R, Yamaguchi T, Matsumoto K, Tojo SJ, Tamatani T, Kitajima M, Makino N, Ishimura Y, Suematsu M: Inducation of heme oxygenase-1 suppresses venular leukocyte adhesion elicited by oxidative stress: role of bilirubin generated by the enzyme. Circ Res, 85: 663-671, 1999. – reference: 24) Lee TS, Chang CC, Zhu Y, Shyy JY: Simvastatin induces heme oxygenase-1: a novel mechanism of vessel protection. Circulation, 110: 1296-1302, 2004. – reference: 14) Makino N, Suematsu M, Sugiura Y, Morikawa H, Shiomi S, Goda N, Sana T, Nimura Y, Sugimachi K, Ishimura Y: Altered expression of heme oxygenase-1 in the livers of patients with portal hypertensive diseases. Hepatology, 33: 32-42, 2001. – reference: 11) Takeda Y, Takeno M, Iwasaki M, Kobayashi H, Kirino Y, Ueda A, Nagahama K, Aoki I, Ishigatsubo Y: Chemical induction of HO-1 suppresses lupus nephritis by reducing local iNOS expression and synthesis of anti-dsDNA anti-body. Clin Exp Immunol, 138: 237-244, 2004. – reference: 19) Kirino Y, Takeno M, Iwasaki M, Ueda A, Ohno S, Shirai A, Kanamori H, Tanaka K, Ishigatsubo Y: Increased serum HO-1 in hemophagocytic syndrome and adult-onset Still's disease: Use in the differential diagnosis of hyperterritinemia. Arthritis Res Ther, 7: R616-R624, 2005. – reference: 21) Dong Z, Lavrovsky Y, Venkatachalam MA, Roy AK: Heme oxygenase-1 in tissue pathology: the Yin and Yang. Am J Pathol, 156: 1485-1488, 2000. – reference: 23) Kataoka K, Handa H, Nishizawa M: Induction of cellular antioxidative stress genes through heterodimeric transcription factor Nrf2/small Maf by antirheumatic gold (I) compounds. J Biol Chem, 276: 34074-34081, 2001. – reference: 20) Suttner DM, Dennery PA: Reversal of HO-1 related cytoprotection with increased expression is due to reactive iron. FASEB J, 13: 1800-1809, 1999. – reference: 17) Lee TS, Tsai HL, Chau LY: Induction of heme oxygenase-1 expression in murine macrophages is essential for the anti-inflammatory effect of low dose 15-deoxy-Delta12,14-prostaglandin J2. J Biol Chem, 278: 19325-19330, 2003. – reference: 18) Yachie A, Toma T, Mizuno K, Okamoto H, Shimura S, Ohta K, Kasahara Y, Koizumi S: Heme oxygenase-1 production by peripheral blood monocytes during acute inflammatory illnesses of children. Exp Biol Med, 228: 550-556, 2003. – reference: 13) Yachie A, Niida Y, Wada T, Igarashi N, Kaneda H, Toma T, Ohta K, Kasahara Y, Koizumi S: Oxidative stress causes enhanced endothelial cell injury in human heme oxygenase-1 deficiency. J Clin Invest, 103: 129-135, 1999. – reference: 1) Morse D, Choi AM: Heme oxygenase-1: the “emerging molecule” has arrived. Am J Respir Cell Mol Biol, 27: 8-16, 2002. – reference: 4) Suematsu M, Goda N, Sano T, Kashiwagi S, Egawa T, Shinoda Y, Ishimura Y: Carbon monoxide: an endogenous modulator of sinusoidal tone in the perfused rat liver. J Clin Invest, 96: 2431-2437, 1995. – reference: 15) Mayerhofer M, Florian S, Krauth MT, Aichberger KJ, Bilban M, Marculescu R, Printz D, Fritsch G, Wagner O, Selzer E, Sperr WR, Valent P, Sillaber C: Identification of heme oxygenase-1 as a novel BCR/ABL-dependent survival factor in chronic myeloid leukemia. Cancer Res, 64: 3148-3154, 2004. – reference: 16) Schipper HM, Chertkow H, Mehindate K, Frankel D, Melmed C, Bergman H: Evaluation of heme oxygenase-1 as a systemic biological marker of sporadic AD. Neurology, 54: 1297-1304, 2000. – reference: 9) Tsuburai T, Suzuki M, Nagashima Y, Suzuki S, Inoue S, Hasiba T, Ueda A, Ikehara K, Matsuse T, Ishigatsubo Y: Adenovirus-mediated transfer and overexpression of heme oxygenase 1 cDNA in lung prevents bleomycin-induced pulmonary fibrosis via a Fas-Fas ligand-independent pathway. Hum Gene Ther, 13: 1945-1960, 2002. – reference: 6) Harrison PM, Arosio P: The ferritins: molecular properties, iron storage function and cellular regulation. Biochim Biophys Acta, 1275: 161-203, 1996. – reference: 25) 吉川敏一, 内藤裕二 : 炎症と活性酸素, 一酸化窒素 (NO), 一酸化炭素 (CO)―炎症性腸疾患を中心に―. 炎症・再生, 24(5): 545-552, 2004. – reference: 8) Hashiba T, Suzuki M, Nagashima Y, Suzuki S, Inoue S, Tsuburai T, Matsuse T, Ishigatubo Y: Adenovirus-mediated transfer of heme oxygenase-1 cDNA attenuates severe lung injury induced by the influenza virus in mice. Gene Ther, 8: 1499-1507, 2001. – reference: 3) Morita T, Perrella MA, Lee ME, Kourembanas S: Smooth muscle cell-derived carbon monoxide is a regulator of vascular cGMP. Proc Natl Acad Sci USA, 92: 1475-1479, 1995. – reference: 7) Inoue S, Suzuki M, Nagashima Y, Suzuki S, Hashiba T, Tsuburai T, Ikehara K, Matsuse T, Ishigatsubo Y: Transfer of heme oxygenase 1 cDNA by a replication-deficient adenovirus enhances interleukin 10 production from alveolar macrophages that attenuates lipopolysaccharide-induced acute lung injury in mice. Hum Gene Ther, 12: 967-979, 2001. – reference: 2) Sun J, Brand M, Zenke Y, Tashiro S, Groudine M, Igarashi K: Heme regulates the dynamic exchange of Bach1 and NF-E2-related factors in the Maf transcription factor network. Proc Natl Acad Sci USA, 101: 1461-1466, 2004. – reference: 10) Tsuburai T, Kaneko T, Nagashima Y, Ueda A, Tagawa A, Shinohara T, Ishigatsubo Y: Pseudomonas aeruginosa-induced neutrophilic lung inflammation is attenuated by adenovirus-mediated transfer of the heme oxygenase 1 cDNA in mice. Hum Gene Ther, 15: 273-285, 2004. |
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| Title | 炎症性疾患におけるHeme oxygenase-1 (HO-1) の発現 |
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