1998 Fiscal Year Annual Research Report

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

Research Project

Project/Area Number	10181219
Research Institution	Kyushu University
Principal Investigator	仁保喜之九州大学, 医学部, 教授 (60091287)
Co-Investigator(Kenkyū-buntansha)	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)
Keywords	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
Research Abstract	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。

Research Products
(26 results)

All Other

All Publications (26 results)

[Publications] Niho Y.: "Role of IL-10 in the crossregulation of prostaglandins and cytokines in monocytes." Acta Haematol.99. 165-170 (1998)
[Publications] Niho Y.: "Fas/Fas ligand and hematopoietic progenior cells." Curr.Opin.Hematol.5・3. 163-165 (1998)
[Publications] 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)
[Publications] 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)
[Publications] Yamaoka K.: "Activation of STAT5 by lipopolysaccharide through granulocyte-macrophage colony-stimulating factor production in human monocytes." J.Immunol.160. 838-845 (1998)
[Publications] Horiuchi T.: "A non-sense mutation at arg^<95> is predominant in complement 9 deficiency in Japanese." J.Immunol.160. 1509-1513 (1998)
[Publications] 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)
[Publications] 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)
[Publications] Kojima T.: "Genetic basis of human complement C8α-γ deficiency." J.Immunol. 161・7. 3763-3766 (1998)
[Publications] 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)
[Publications] Otsuka T.: "Growth inhibition of leukemic cells by(-)-epigallocatechim gallate,the main constituent of green tea." Life Sciences. 63・16. 1397-1403 (1998)
[Publications] 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)
[Publications] Tokunaga Y.: "Effect of thrombopoietin on proliferation of blasts from CD7-positive acute myclogenous leukaemia." Br.J.Haematol. 102. 1232-1240 (1998)
[Publications] Higuchi M.: "Analysis of CD40 ligand gene mutations in patients with primary biliary cirrhosis." Scand.J.Clin.Lab.Invest.58. 429-432 (1998)
[Publications] 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)
[Publications] Akashi T.: "Proliferation of CD3 B220 single-positive normal T cell was suppressed in B-cell-deficient lpr mice." Immunology. 93. 238-248 (1998)
[Publications] 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)
[Publications] Nagafuchi S.: "Intrademal administration of viral vaccines." Rev.Med.Virol.8. 97-111 (1998)
[Publications] 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)
[Publications] 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)
[Publications] Kuroiwa M.: "Interferon-alpha thrapy for chronic myelogenous leukemia during prefnancy." Am.J.Hematology. 59・1. 101-102 (1998)
[Publications] Ishikawa F.: "Autoreactive antibodies following autologous peripheral blood stem cell transplantation." Bone Marrow Transplant.22. 729-731 (1998)
[Publications] 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)
[Publications] Asano Y.: "Effect of Interleukin-10 on the hematopoietic progenitor cells from patients with aplastic anemia." Stem cells. in press. (1999)
[Publications] Niho Y.: "Molecular and genetic approches to disease." Kyushu Univ.Press(Editor:Yoshiyuki Niho), 198 (1998)
[Publications] 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 Fiscal Year Annual Research Report

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

Principal Investigator

仁保 喜之 九州大学, 医学部, 教授 (60091287)

Research Products

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

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

[Publications] 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)

[Publications] 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)

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

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

[Publications] 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)

[Publications] 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)

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

[Publications] 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)

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

[Publications] 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)

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

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

[Publications] 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)

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

[Publications] 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)

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

[Publications] 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)

[Publications] 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)

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

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

[Publications] 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)

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

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

[Publications] 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)

仁保喜之九州大学, 医学部, 教授 (60091287)