2000 Fiscal Year Annual Research Report

インターロイキン15産生における遺伝子転写後調節機構の解明

Research Project

Project/Area Number	11770168
Research Institution	Nagoya University
Principal Investigator	西村仁志名古屋大学, 医学部, 助手 (00283440)
Keywords	インターロイキン / 転写調節 / 細菌感染症 / IL-15 / アミノ酸翻訳 / リーダーペプチド
Research Abstract	インターロイキン(IL)-15遺伝子の発現は、心臓、肺、肝臓、腎臓、および骨格筋なと、多くの臓器や組織に認められる。さらに、単球や上皮性および線維芽性細胞株に高い発現が見られ、活性化T細胞やB細胞などのリンパ球系の細胞には認められない。我々はSalmonellaをはじめさまざまな細菌感染症において、IL-15遺伝子の発現が高まることを見い出した。我々は、感染時に発現するIL-15遺伝子の転写調節の分子機構を調べる目的でマウスのゲノムDNAライブラリーからIL-15エクソン1の5'上流部分をクローニングし、マクロファージにおける転写活性化機構について解析した。この領域はマクロファージをLPS刺激した際に転写を活性化することから、プロモーター活性を持つことがわかった。このプロモーターには典型的なTATAボックスは存在せず、SPム1が結合するGCボックスを持っていた。このことから、IL-15遺伝子は多くのTATAレス遺伝子に認められるような、ハウスキーピング遺伝子の可能性が示唆される。さらに、この領域には、多くの炎症性サイトカインのプロモーター上に認められるNF-kB,NF-IL-6,IRFの結合モチーフが存在する。これらのうち、どの領域がマクロファージ内でのIL-15遺伝子の発現に重要が決定したところ、NF-kB結合領域であることを明らかにした。IL-15のmRNAには、選択的スプライシングによって少なくとも2種類のアイソフォームが存在する6)。興味深いことに、両者のmRNAはIL-15の成熟型アミノ酸をコードしているが、リーダーペプチドが分泌型あるいは非分泌型のものに分かれる。また、IL-15の翻訳物のC末端によっても産生調節が行われているとした報告もなされている。このように、IL-15の産生には転写、アミノ酸翻訳、分泌の各段階で制御されている。しかし、感染によってこれらの転写後修飾に変化が生じるかどうかは明らかではない。

Research Products

(27 results)

All Other

All Publications (27 results)

[Publications] Yamada,K.: "Characterization of CD4^+CD8αα^+andCD4^-CD8αα^+intestinal intraepithelial lymphocytes in rats."Int.Immunol.,. 11. 21-28 (1999)
[Publications] Nishimura,H.: "MHC class II-dependent NK1.1^+γδ T cells are induced in mice by Salmonella infection."J.Immunol.. 162. 1573-1581 (1999)
[Publications] Kimura,K.: "Immunogene therapy for murine fibrosarcoma using IL-15 gene with high translation efficiency."Eur.J.Immunol.. 29. 1532-1542 (1999)
[Publications] Ishigami,M.: "The roles of intrahepatic Vα 14^+NK1.1^+T cells for liver injury induced by Salmonella infection."Hepatology. 29. 1799-1808 (1999)
[Publications] Ishigami,M.: "The roles of intrahepatic γδ- T cells for liver injury in mouse induced by Salmonella infection."Microbiol.Immunol.. 43. 461-470 (1999)
[Publications] Mitani,A.: "Interleukin-15 might be responsible for early activation of intestinal intraepithelial lymphocytes after oral infection with Listeria monocytogenes in mice."Immunolgy. 97. 92-99 (1999)
[Publications] Naiki,Y.: "Regulatory role of peritoneal NK1.1^+αβ T cells in IL-12 production during Salmonella infection."J.Immunol.. 163. 2057-2063 (1999)
[Publications] Mokuno,Y.: "Prostaglandin E1 protects against liver injury induced by Escherichia coli infection via a dominant Th2-like response of liver T cells in mice."Hepatology. 30. 1464-1472 (1999)
[Publications] Hirose,K.: "Endogenous IL-15 might be responsible for early protection by natural killer cells against infection with an avirulent strain of Salmonella choleraesuis in mice."J.Leukocyte Biol.. 66. 382-390 (1999)
[Publications] Mayumi,T.: "IL-15 is elevated in the patients of postoperative enterocllitis."Cytokine. 11. 888-893 (1999)
[Publications] Tanaka,S.: "Activation of T cells recognizing an epitope of heat shock protein (HSP) 70 can protect against rat adjuvant arthritis."J.Immunol.. 163. 5560-5565. (1999)
[Publications] Nishimura,H.: "Differential roles of IL-15 mRNA isoforms Generated by alternative splicing in immune responses in vivo."J.Exp.Med.. 191. 157-169 (2000)
[Publications] Liu,T.: "Difference in interleukin-12 and-15 production by dendritic cells at the early stage of Listeria monocytogenes infection between BALB/c and C57 BL/6 mice。"Cell.Immunol.. 202. 31-40 (2000)
[Publications] Naiki,Y.: "γδ T cells may dichotomously modulate infection with avirulent Salmonella choleraesuis via IFN-γ and IL-13 in mice."Cell.Immunol.. 49. 157-164 (2000)
[Publications] Mokuno,Y.: "Expression of Toll-like receptor 2 on γδ T cells bearing invariant Vγ6/Vδ1 induced by Escherichia coli infection."J.Immunol.. 165. 931-940 (2000)
[Publications] Umemura,M.: "Expression of mouse mammary tumor virus superantigen accelerates tumorgenicity of myeloma cells."Journal of Virology. 74. 8226-8233 (2000)
[Publications] Tsunobuchi,H.: "A protective role of interleukin-15 in a mouse model for systemic infection with herpes simplex virus."Virology. 275. 57-66 (2000)
[Publications] Kimura,K.: "Synergistic effect of IL-15 and IL-12 on anti-tumor activity in a murine malignant pleurisy model."Cancer Immunol.Immun.. 49. 71-77 (2000)
[Publications] Tsunobuchi,H.: "Memory Type CD8^+T cells protect IL-2R α-deficient mice from systemic infection with HSV Type 2."J.Immunol.. 165. 6682-6686 (2000)
[Publications] Ishimitsu,R.: "Overexpression of Interleukin-15 in vivo enhances Tcl response which inhibits allerqic inflammation in a murine model of asthma."J.Immunol.. 166. 1991-2001 (2001)
[Publications] Umemura,M.: "Impaired IL-15 production in murine AIDS mice might underlie susceptibility to mycobacterial infection."J.Leuko.Biol.. 69. 138-148 (2001)
[Publications] Umemura,M.: "Overexpression of IL-15 in vivo induces a predominant Tcl response in mice inoculated with Mycobacterium bovis Bacille Calmette-Guerin infection."J.Immunol.. in press.. (2001)
[Publications] Hara,T.: "Thymus-dependent modulation of Ly49 inhibitory receptor expression on NK1.1^+γ/δ T cells."Immunology. in press.. (2001)
[Publications] 西村仁志: "IL-15の生物活性と産生調節"Ann.Rev.免疫. 1999. 119-125 (1999)
[Publications] 西村仁志: "The γ δT-cell bridge"Ann.Rev.免疫. 1999. 41-47 (1999)
[Publications] 西村仁志: "生体防御機構とIL-15"バイオサイエンスとバイオインダストリー. 57. 297-302 (1999)
[Publications] 西村仁志: "IL-15Rα"臨床免疫. 34. 613-620 (2000)

2000 Fiscal Year Annual Research Report

インターロイキン15産生における遺伝子転写後調節機構の解明

Principal Investigator

西村 仁志 名古屋大学, 医学部, 助手 (00283440)

Research Products

[Publications] Yamada,K.: "Characterization of CD4^+CD8αα^+andCD4^-CD8αα^+intestinal intraepithelial lymphocytes in rats."Int.Immunol.,. 11. 21-28 (1999)

[Publications] Nishimura,H.: "MHC class II-dependent NK1.1^+γδ T cells are induced in mice by Salmonella infection."J.Immunol.. 162. 1573-1581 (1999)

[Publications] Kimura,K.: "Immunogene therapy for murine fibrosarcoma using IL-15 gene with high translation efficiency."Eur.J.Immunol.. 29. 1532-1542 (1999)

[Publications] Ishigami,M.: "The roles of intrahepatic Vα 14^+NK1.1^+T cells for liver injury induced by Salmonella infection."Hepatology. 29. 1799-1808 (1999)

[Publications] Ishigami,M.: "The roles of intrahepatic γδ- T cells for liver injury in mouse induced by Salmonella infection."Microbiol.Immunol.. 43. 461-470 (1999)

[Publications] Mitani,A.: "Interleukin-15 might be responsible for early activation of intestinal intraepithelial lymphocytes after oral infection with Listeria monocytogenes in mice."Immunolgy. 97. 92-99 (1999)

[Publications] Naiki,Y.: "Regulatory role of peritoneal NK1.1^+αβ T cells in IL-12 production during Salmonella infection."J.Immunol.. 163. 2057-2063 (1999)

[Publications] Mokuno,Y.: "Prostaglandin E1 protects against liver injury induced by Escherichia coli infection via a dominant Th2-like response of liver T cells in mice."Hepatology. 30. 1464-1472 (1999)

[Publications] Hirose,K.: "Endogenous IL-15 might be responsible for early protection by natural killer cells against infection with an avirulent strain of Salmonella choleraesuis in mice."J.Leukocyte Biol.. 66. 382-390 (1999)

[Publications] Mayumi,T.: "IL-15 is elevated in the patients of postoperative enterocllitis."Cytokine. 11. 888-893 (1999)

[Publications] Tanaka,S.: "Activation of T cells recognizing an epitope of heat shock protein (HSP) 70 can protect against rat adjuvant arthritis."J.Immunol.. 163. 5560-5565. (1999)

[Publications] Nishimura,H.: "Differential roles of IL-15 mRNA isoforms Generated by alternative splicing in immune responses in vivo."J.Exp.Med.. 191. 157-169 (2000)

[Publications] Liu,T.: "Difference in interleukin-12 and-15 production by dendritic cells at the early stage of Listeria monocytogenes infection between BALB/c and C57 BL/6 mice。"Cell.Immunol.. 202. 31-40 (2000)

[Publications] Naiki,Y.: "γδ T cells may dichotomously modulate infection with avirulent Salmonella choleraesuis via IFN-γ and IL-13 in mice."Cell.Immunol.. 49. 157-164 (2000)

[Publications] Mokuno,Y.: "Expression of Toll-like receptor 2 on γδ T cells bearing invariant Vγ6/Vδ1 induced by Escherichia coli infection."J.Immunol.. 165. 931-940 (2000)

[Publications] Umemura,M.: "Expression of mouse mammary tumor virus superantigen accelerates tumorgenicity of myeloma cells."Journal of Virology. 74. 8226-8233 (2000)

[Publications] Tsunobuchi,H.: "A protective role of interleukin-15 in a mouse model for systemic infection with herpes simplex virus."Virology. 275. 57-66 (2000)

[Publications] Kimura,K.: "Synergistic effect of IL-15 and IL-12 on anti-tumor activity in a murine malignant pleurisy model."Cancer Immunol.Immun.. 49. 71-77 (2000)

[Publications] Tsunobuchi,H.: "Memory Type CD8^+T cells protect IL-2R α-deficient mice from systemic infection with HSV Type 2."J.Immunol.. 165. 6682-6686 (2000)

[Publications] Ishimitsu,R.: "Overexpression of Interleukin-15 in vivo enhances Tcl response which inhibits allerqic inflammation in a murine model of asthma."J.Immunol.. 166. 1991-2001 (2001)

[Publications] Umemura,M.: "Impaired IL-15 production in murine AIDS mice might underlie susceptibility to mycobacterial infection."J.Leuko.Biol.. 69. 138-148 (2001)

[Publications] Umemura,M.: "Overexpression of IL-15 in vivo induces a predominant Tcl response in mice inoculated with Mycobacterium bovis Bacille Calmette-Guerin infection."J.Immunol.. in press.. (2001)

[Publications] Hara,T.: "Thymus-dependent modulation of Ly49 inhibitory receptor expression on NK1.1^+γ/δ T cells."Immunology. in press.. (2001)

[Publications] 西村仁志: "IL-15の生物活性と産生調節"Ann.Rev.免疫. 1999. 119-125 (1999)

[Publications] 西村仁志: "The γ δT-cell bridge"Ann.Rev.免疫. 1999. 41-47 (1999)

[Publications] 西村仁志: "生体防御機構とIL-15"バイオサイエンスとバイオインダストリー. 57. 297-302 (1999)

[Publications] 西村仁志: "IL-15Rα"臨床免疫. 34. 613-620 (2000)

西村仁志名古屋大学, 医学部, 助手 (00283440)