1998 年度実績報告書

サイトカインを介した造血幹細胞の増殖と分化の制御機構の解析

研究課題

研究課題/領域番号	10181219
研究機関	九州大学
研究代表者	仁保喜之九州大学, 医学部, 教授 (60091287)
研究分担者	浅野嘉延九州大学, 医学部, 助手 (60271110) 権藤久司九州大学, 医学部, 助手 (10253428) 岡村孝九州大学, 医学部, 助手 (30136436)
キーワード	G-CSF / G-CSF受容体 / 細胞内シグナル伝達蛋白 / 転写因子 / 先天性好中球減少症 / 骨髄性白血病
研究概要	G-CSFは好中球系細胞の増殖、分化、機能発現、アポトーシスを調節しているサイトカインである。そこで、本研究では、好中球系造血に破綻を来した種々の造血異常症におけるG-CSF受容体および細胞内シグナル伝達蛋白の遺伝子解析を行ない、病態との相関からヒト造血におけるG-CSF刺激伝達系を遺伝子レベルで明らかにすることを目的とした。最初に、先天性好中球減少症の1例において、G-CSF受容体膜貫通部近傍の増殖シグナル領域に構造異常を発見した。この変異G-CSF受容体を遺伝子導入したLGM-1細胞はG-CSFに対する増殖反応性が著しく不良であり、分化成熟能は比較的保たれていた。一方、分化成熟シグナル伝達に必須であるG-CSF受容体細胞内領域のC末端側が欠損した先天性好中球減少症の症例も経験した。そこで現在は、増殖シグナル領域および分化成熟シグナル領域に変異のあるG-CSF受容体をそれぞれ細胞に遺伝子導入し、細胞内シグナル伝達蛋白のリン酸化を観察するなど純粋な実験系で比較検討を行なっている。この方法により、G-CSFの機能に特異的な刺激伝達系の解析が可能となった。一方、複数例の骨髄性白血病においてもG-CSF受容体およびJak l、Jak 2、Tyk 2の遺伝子解析を行なったが、これまでに病態と関連する遺伝子変異は発見できていない。現在は、CFLPなどを用いて多数例で遺伝子解析を繰り返すとともに、転写因子にも範囲を広げて検索を行なっている。先行実験の結果では、白血病細胞においてStat 3のisoformの遺伝子発現に不均衡を認め、詳細な解析を急いでいる。以上の研究結果は、ヒト造血におけるG-CSF刺激伝達系の一端を解明する手掛かりになるとともに、造血異常症の病態解明にも大きく寄与することとが期待される。

研究成果
(26件)

すべてその他

すべて文献書誌 (26件)

[文献書誌] Niho Y.: "Role of IL-10 in the crossregulation of prostaglandins and cytokines in monocytes." Acta Haematol.99. 165-170 (1998)
[文献書誌] Niho Y.: "Fas/Fas ligand and hematopoietic progenior cells." Curr.Opin.Hematol.5・3. 163-165 (1998)
[文献書誌] Shibata S.: "Analysis of the granulocyte colony-stimulating foctor receptor gene structure using PCR-SSCP in myeloid leukemia and myelodysplastic syndrome." Eur.J.Haematol.60. 197-201 (1998)
[文献書誌] Kanaji T.: "A common genetic polymorphism (46 C to T substituition)in the 5'-untranslated region of the coagulation factor XII gene is associated with low translation efficiency and decrease in plasma factor XII level." Blood. 91・6. 2010-2014 (1998)
[文献書誌] Yamaoka K.: "Activation of STAT5 by lipopolysaccharide through granulocyte-macrophage colony-stimulating factor production in human monocytes." J.Immunol.160. 838-845 (1998)
[文献書誌] Horiuchi T.: "A non-sense mutation at arg^<95> is predominant in complement 9 deficiency in Japanese." J.Immunol.160. 1509-1513 (1998)
[文献書誌] Fujishima H.: "Interferon-α and -γ inhibit the growth and neoplastic potential of V-src-transformed human epithelial cells by reducing src tyrosine kinase activity." Int.J.Cancer. 76. 423-429 (1998)
[文献書誌] Niiro H.: "MAP kinase pathways as a route for regulatory mechanisms of IL-10 and IL-4 which inhibit COX-2 expression in human monocytes." Biochem.Bioph.Re.Co.250. 200-205 (1998)
[文献書誌] Kojima T.: "Genetic basis of human complement C8α-γ deficiency." J.Immunol. 161・7. 3763-3766 (1998)
[文献書誌] Murakami Y.: "Constitutive activation of Jak-2 in and Tyk-2 in a v-Src-transformed human gallbladder adenocarcinoma cell line." J.Cell Physiol.175. 220-228 (1998)
[文献書誌] Otsuka T.: "Growth inhibition of leukemic cells by(-)-epigallocatechim gallate,the main constituent of green tea." Life Sciences. 63・16. 1397-1403 (1998)
[文献書誌] Asano Y.: "Action of interleukin-3 on the prolideration of leukaemic progenitor cells from patients with acute myeloblastic leukaemia." Clin.Lab.Haematol.20. 225-229 (1998)
[文献書誌] Tokunaga Y.: "Effect of thrombopoietin on proliferation of blasts from CD7-positive acute myclogenous leukaemia." Br.J.Haematol. 102. 1232-1240 (1998)
[文献書誌] Higuchi M.: "Analysis of CD40 ligand gene mutations in patients with primary biliary cirrhosis." Scand.J.Clin.Lab.Invest.58. 429-432 (1998)
[文献書誌] Ichiki Y.: "Analysis of T-cell receptor β of the T-cell clones reactive to the human PDC-E2 163-176 peputide in the context od HLA-DR53 in patients with primary biliary cirrhosis." Hepatology. 26・3. 728-733 (1998)
[文献書誌] Akashi T.: "Proliferation of CD3 B220 single-positive normal T cell was suppressed in B-cell-deficient lpr mice." Immunology. 93. 238-248 (1998)
[文献書誌] Kimura Y.: "Attachment of hepatitis C virus to cultured cells:A novel predictive factor for successful interferon therapy." J.Med.Virology. 56. 25-32 (1998)
[文献書誌] Nagafuchi S.: "Intrademal administration of viral vaccines." Rev.Med.Virol.8. 97-111 (1998)
[文献書誌] Miyamoto T.: "Early viral complications following CD34-selected autologous periphaeral blood stem cell transplantation for non-Hodgkin's lymphoma." Br.J.Haematol.100. 348-350 (1998)
[文献書誌] Nagafuji K.: "Donor lymphocyte transfusion for the treatment of Epstein-Barr virus-associated lymphoproliferative disorder of the brain." Bone Marrow Transplant. 21. 1155-1158 (1998)
[文献書誌] Kuroiwa M.: "Interferon-alpha thrapy for chronic myelogenous leukemia during prefnancy." Am.J.Hematology. 59・1. 101-102 (1998)
[文献書誌] Ishikawa F.: "Autoreactive antibodies following autologous peripheral blood stem cell transplantation." Bone Marrow Transplant.22. 729-731 (1998)
[文献書誌] Okamura K.: "Identification of a novel bovine serum protein which is involved in human T-cell leukemia virus type I(HTLV-1)-induced syncytium formation." Arch.Virol.144. 1-18 (1999)
[文献書誌] Asano Y.: "Effect of Interleukin-10 on the hematopoietic progenitor cells from patients with aplastic anemia." Stem cells. in press. (1999)
[文献書誌] Niho Y.: "Molecular and genetic approches to disease." Kyushu Univ.Press(Editor:Yoshiyuki Niho), 198 (1998)
[文献書誌] 仁保喜之: "内科学進歩のトピックス" 九州大学出版会(編集:仁保喜之,石橋大海), 394 (1998)

1998 年度 実績報告書

サイトカインを介した造血幹細胞の増殖と分化の制御機構の解析

研究代表者

仁保 喜之 九州大学, 医学部, 教授 (60091287)

研究成果

[文献書誌] Niho Y.: "Role of IL-10 in the crossregulation of prostaglandins and cytokines in monocytes." Acta Haematol.99. 165-170 (1998)

[文献書誌] Niho Y.: "Fas/Fas ligand and hematopoietic progenior cells." Curr.Opin.Hematol.5・3. 163-165 (1998)

[文献書誌] Shibata S.: "Analysis of the granulocyte colony-stimulating foctor receptor gene structure using PCR-SSCP in myeloid leukemia and myelodysplastic syndrome." Eur.J.Haematol.60. 197-201 (1998)

[文献書誌] Kanaji T.: "A common genetic polymorphism (46 C to T substituition)in the 5'-untranslated region of the coagulation factor XII gene is associated with low translation efficiency and decrease in plasma factor XII level." Blood. 91・6. 2010-2014 (1998)

[文献書誌] Yamaoka K.: "Activation of STAT5 by lipopolysaccharide through granulocyte-macrophage colony-stimulating factor production in human monocytes." J.Immunol.160. 838-845 (1998)

[文献書誌] Horiuchi T.: "A non-sense mutation at arg^<95> is predominant in complement 9 deficiency in Japanese." J.Immunol.160. 1509-1513 (1998)

[文献書誌] Fujishima H.: "Interferon-α and -γ inhibit the growth and neoplastic potential of V-src-transformed human epithelial cells by reducing src tyrosine kinase activity." Int.J.Cancer. 76. 423-429 (1998)

[文献書誌] Niiro H.: "MAP kinase pathways as a route for regulatory mechanisms of IL-10 and IL-4 which inhibit COX-2 expression in human monocytes." Biochem.Bioph.Re.Co.250. 200-205 (1998)

[文献書誌] Kojima T.: "Genetic basis of human complement C8α-γ deficiency." J.Immunol. 161・7. 3763-3766 (1998)

[文献書誌] Murakami Y.: "Constitutive activation of Jak-2 in and Tyk-2 in a v-Src-transformed human gallbladder adenocarcinoma cell line." J.Cell Physiol.175. 220-228 (1998)

[文献書誌] Otsuka T.: "Growth inhibition of leukemic cells by(-)-epigallocatechim gallate,the main constituent of green tea." Life Sciences. 63・16. 1397-1403 (1998)

[文献書誌] Asano Y.: "Action of interleukin-3 on the prolideration of leukaemic progenitor cells from patients with acute myeloblastic leukaemia." Clin.Lab.Haematol.20. 225-229 (1998)

[文献書誌] Tokunaga Y.: "Effect of thrombopoietin on proliferation of blasts from CD7-positive acute myclogenous leukaemia." Br.J.Haematol. 102. 1232-1240 (1998)

[文献書誌] Higuchi M.: "Analysis of CD40 ligand gene mutations in patients with primary biliary cirrhosis." Scand.J.Clin.Lab.Invest.58. 429-432 (1998)

[文献書誌] Ichiki Y.: "Analysis of T-cell receptor β of the T-cell clones reactive to the human PDC-E2 163-176 peputide in the context od HLA-DR53 in patients with primary biliary cirrhosis." Hepatology. 26・3. 728-733 (1998)

[文献書誌] Akashi T.: "Proliferation of CD3 B220 single-positive normal T cell was suppressed in B-cell-deficient lpr mice." Immunology. 93. 238-248 (1998)

[文献書誌] Kimura Y.: "Attachment of hepatitis C virus to cultured cells:A novel predictive factor for successful interferon therapy." J.Med.Virology. 56. 25-32 (1998)

[文献書誌] Nagafuchi S.: "Intrademal administration of viral vaccines." Rev.Med.Virol.8. 97-111 (1998)

[文献書誌] Miyamoto T.: "Early viral complications following CD34-selected autologous periphaeral blood stem cell transplantation for non-Hodgkin's lymphoma." Br.J.Haematol.100. 348-350 (1998)

[文献書誌] Nagafuji K.: "Donor lymphocyte transfusion for the treatment of Epstein-Barr virus-associated lymphoproliferative disorder of the brain." Bone Marrow Transplant. 21. 1155-1158 (1998)

[文献書誌] Kuroiwa M.: "Interferon-alpha thrapy for chronic myelogenous leukemia during prefnancy." Am.J.Hematology. 59・1. 101-102 (1998)

[文献書誌] Ishikawa F.: "Autoreactive antibodies following autologous peripheral blood stem cell transplantation." Bone Marrow Transplant.22. 729-731 (1998)

[文献書誌] Okamura K.: "Identification of a novel bovine serum protein which is involved in human T-cell leukemia virus type I(HTLV-1)-induced syncytium formation." Arch.Virol.144. 1-18 (1999)

[文献書誌] Asano Y.: "Effect of Interleukin-10 on the hematopoietic progenitor cells from patients with aplastic anemia." Stem cells. in press. (1999)

[文献書誌] Niho Y.: "Molecular and genetic approches to disease." Kyushu Univ.Press(Editor:Yoshiyuki Niho), 198 (1998)

[文献書誌] 仁保喜之: "内科学進歩のトピックス" 九州大学出版会(編集:仁保喜之,石橋大海), 394 (1998)

1998 年度実績報告書

仁保喜之九州大学, 医学部, 教授 (60091287)