1993 Fiscal Year Annual Research Report

炎症性サイトカインのin vitro及びin vivoでの発現機序の解析とその制御

Research Project

Project/Area Number	04671366
Research Institution	Jichi Medical School, Department of Medicine Grant-in-Aid for Scientific Research(C)
Principal Investigator	笠原忠自治医科大学, 医学部/助教授 (60049096)
Co-Investigator(Kenkyū-buntansha)	高余洲自治医科大学, 医学部, 助手 (30234686) 向田直史金沢大学, がん研, 助教授 (30182067)
Keywords	炎症性サイトカイン / IL-8 / MCAF(MCP-1) / 好中球ケモタクシス / 尿中サイトカイン
Research Abstract	私共はIL-1やTNFによって誘導されるIL-8,MCAFなどの炎症性サイトカインがn vitroおよびin vivoでの生体防禦機構に重要な役割を果たしていると考え本研究を行い、以下のような成果が得た。 (1)In vitroにおけるIL-1,TNFによる炎症性サイトカイン遺伝子発現誘導とその制御機序の解析:我々はIL-1やTNFおよびLPSがヒトの培養細胞(神経系、線維芽細胞株など)に対し、IL-8,MCAFなどの炎症性サイトカイン遺伝子を速やかに発現誘導することを見いだした。これらの細胞株における炎症性サイトカイン遺伝子発現とグルココルチコイドによる遺伝子発現の制御、とくに発現制禦蛋白(NF-kappaB,C/EBP,NF-IL-6,AP-1)の同定をゲルシフトアッセイにより明らかにした。 (2)種々の疾患における炎症性サイトカインの関与とその動態解析:我々はすでに、IL-8,MCAFに対するMoAbの作製と酵素免疫測定法を確立した。種々の感染症(尿路感染、子宮内感染症、髄膜炎など)および炎症性疾患(慢性関節リューマチ、免疫賦活剤投与癌患者、心筋梗塞および過敏性肺臓炎など)患者体液中のIL-8,MCAFレベルをELISA,RIA法で測定し、その臨床的意義づけを行った。 MCAFの大量発現とin vivoにおける感染防御作用:動物細胞由来のヒトMCAFを大量に発現させ、マウスにおけるSalmonella,Pseudomonas感染に対する防禦能がを検討したところ、予めを投与したマウスでは明らかな防御作用があることが知られた。MCAFはin vitroでもマクロファージによる貧食および殺菌作用があることが示され、MAFとして働くことがわかった。現在さらに、MCAFcDNAを導入した腫瘍細胞を作成し、in vivoにおける抗腫瘍増殖効果を検討しているところである。

Research Products

(20 results)

All Other

All Publications (20 results)

[Publications] Ko,Y-C.: "Establishment of a sensitive enzyme-linked immunosorbent assay for human IL-8" J.Immunol.Methods. 149. 227-235 (1992)
[Publications] Mukaida,N.: "Molecular analysis of the inhibition of IL-8 production by dexamethasone in a human fibrosar coma cell line." Immunology. 75. 674-679 (1992)
[Publications] Ikeda,U.: "Serum interleukin 6 levels becoe elevated in acute myocardial infarction." J.Mol.Cell.Cardiol.24. 579-584 (1992)
[Publications] Takeda,Y.: "Lobenzarit disodium (CCA)inhibits in vito immunoglobulin production via direct interaction with B lymphocytes" Chem.Pharm.Bull.40. 177-181 (1992)
[Publications] Kikuchi,Y.: "Induction of metallothionein in a human astrocytoma cell Iine by interleukin-1 and heavy metals." FEBS Letters. 317. 22-26 (1993)
[Publications] Ko,Y-C.: "Elevated IL-8 level in the urine of patients with urinary tact infections." Infect.Immunity. 61. 1307-1314 (1993)
[Publications] Saito,S.: "Elevation of amniotic fluid IL-6,IL-8 and granulocyte-colonystimulating factor (G-CSF)in term and preterm parturition." Cytokine. 5. 81-88 (1993)
[Publications] Sato,K.: "Passive immunization with anti-parathyroid hormone-related protein monoclonal antiboby markedly prolongs survival time of" J.Bone Mineral Res.8. 849-860 (1993)
[Publications] Harada,A.: "Expression of recombinant rabbit IL-8 in Escherichia coli and estabilishment of the essential involvement of IL-8 in rocruiting" Intl.Immunol.5. 681-690 (1993)
[Publications] Ikeda,U.: "Expression of intercellular adhesion molecule-1 on rat vascular smooth muscle cells by proinflammatory cytokines." Atherosclerosis. 104. 61-68 (1993)
[Publications] Morita,M.: "Induction and regulation of IL-8 and MCAF mRNAexpression in human glioblastoma and neuroblastoma cell Iines." Eur.Cytokine Netw.4. 351-358 (1993)
[Publications] Tsuchiya,I,: "Induction of inflammatory cytokines in the pleural effusion of cancer patients after the administration of an immunomodulator," Cytokine. (in press). (1993)
[Publications] Nakano,Y.,: "Protection of lethal bacterial infection in mice by monocyte chemotactic and activating factor(MCAF)." Infect. Immunity. (in press). (1994.)
[Publications] Mukaida,N.,: "A novel mechanism of glucocorticoid-mediated gene repression: NF-kB is the target for glucocorticoid-mediated IL-8 gene repression." J.Biol.Chem.(in press). (1994)
[Publications] Sawada,J-I.: "Induction of metallothionein in by cytokines and heavy metalsx" Biological Signals. (in press). (1994)
[Publications] Nielsen,B.W.: "Macrophage-Pathogen Interactions" Marcel-Dekker,New York,ed.by Zwillin,B.S.et al., 131-142 (1994)
[Publications] Hatake,K.: "Molecular Biology Haematopoiesis" Inercept Lyd.Hampshire,ed.by N.G.Abraham,et al.,
[Publications] 笠原忠: "「生体防御」(Maruzen Advanced Technology)" 新井賢一編、丸善、東京, p.95-103, (1992.)
[Publications] 笠原忠: "「生体防御」(Maruzen Advanced Technology)" 新井賢一編、丸善、東京, p.95-103, (1992.)
[Publications] 笠原忠: "「サイトカインと疾病」" 笠倉新平編、日本医学館、東京, p.177-185, (1992)

1993 Fiscal Year Annual Research Report

炎症性サイトカインのin vitro及びin vivoでの発現機序の解析とその制御

Principal Investigator

笠原 忠 自治医科大学, 医学部/助教授 (60049096)

Research Products

[Publications] Ko,Y-C.: "Establishment of a sensitive enzyme-linked immunosorbent assay for human IL-8" J.Immunol.Methods. 149. 227-235 (1992)

[Publications] Mukaida,N.: "Molecular analysis of the inhibition of IL-8 production by dexamethasone in a human fibrosar coma cell line." Immunology. 75. 674-679 (1992)

[Publications] Ikeda,U.: "Serum interleukin 6 levels becoe elevated in acute myocardial infarction." J.Mol.Cell.Cardiol.24. 579-584 (1992)

[Publications] Takeda,Y.: "Lobenzarit disodium (CCA)inhibits in vito immunoglobulin production via direct interaction with B lymphocytes" Chem.Pharm.Bull.40. 177-181 (1992)

[Publications] Kikuchi,Y.: "Induction of metallothionein in a human astrocytoma cell Iine by interleukin-1 and heavy metals." FEBS Letters. 317. 22-26 (1993)

[Publications] Ko,Y-C.: "Elevated IL-8 level in the urine of patients with urinary tact infections." Infect.Immunity. 61. 1307-1314 (1993)

[Publications] Saito,S.: "Elevation of amniotic fluid IL-6,IL-8 and granulocyte-colonystimulating factor (G-CSF)in term and preterm parturition." Cytokine. 5. 81-88 (1993)

[Publications] Sato,K.: "Passive immunization with anti-parathyroid hormone-related protein monoclonal antiboby markedly prolongs survival time of" J.Bone Mineral Res.8. 849-860 (1993)

[Publications] Harada,A.: "Expression of recombinant rabbit IL-8 in Escherichia coli and estabilishment of the essential involvement of IL-8 in rocruiting" Intl.Immunol.5. 681-690 (1993)

[Publications] Ikeda,U.: "Expression of intercellular adhesion molecule-1 on rat vascular smooth muscle cells by proinflammatory cytokines." Atherosclerosis. 104. 61-68 (1993)

[Publications] Morita,M.: "Induction and regulation of IL-8 and MCAF mRNAexpression in human glioblastoma and neuroblastoma cell Iines." Eur.Cytokine Netw.4. 351-358 (1993)

[Publications] Tsuchiya,I,: "Induction of inflammatory cytokines in the pleural effusion of cancer patients after the administration of an immunomodulator," Cytokine. (in press). (1993)

[Publications] Nakano,Y.,: "Protection of lethal bacterial infection in mice by monocyte chemotactic and activating factor(MCAF)." Infect. Immunity. (in press). (1994.)

[Publications] Mukaida,N.,: "A novel mechanism of glucocorticoid-mediated gene repression: NF-kB is the target for glucocorticoid-mediated IL-8 gene repression." J.Biol.Chem.(in press). (1994)

[Publications] Sawada,J-I.: "Induction of metallothionein in by cytokines and heavy metalsx" Biological Signals. (in press). (1994)

[Publications] Nielsen,B.W.: "Macrophage-Pathogen Interactions" Marcel-Dekker,New York,ed.by Zwillin,B.S.et al., 131-142 (1994)

[Publications] Hatake,K.: "Molecular Biology Haematopoiesis" Inercept Lyd.Hampshire,ed.by N.G.Abraham,et al.,

[Publications] 笠原 忠: "「生体防御」(Maruzen Advanced Technology)" 新井賢一編、丸善、東京, p.95-103, (1992.)

[Publications] 笠原 忠: "「生体防御」(Maruzen Advanced Technology)" 新井賢一編、丸善、東京, p.95-103, (1992.)

[Publications] 笠原 忠: "「サイトカインと疾病」" 笠倉新平編、日本医学館、東京, p.177-185, (1992)

笠原忠自治医科大学, 医学部/助教授 (60049096)

[Publications] 笠原忠: "「生体防御」(Maruzen Advanced Technology)" 新井賢一編、丸善、東京, p.95-103, (1992.)

[Publications] 笠原忠: "「生体防御」(Maruzen Advanced Technology)" 新井賢一編、丸善、東京, p.95-103, (1992.)

[Publications] 笠原忠: "「サイトカインと疾病」" 笠倉新平編、日本医学館、東京, p.177-185, (1992)