Regulatory mechanisms of gene expression in anti-inflammatory M2 macrophages

抗炎M2巨噬细胞基因表达的调控机制

• 批准号: 21592371
• 负责人: OHMORI Yoshihiro
• 金额: $ 2.91万
• 依托单位: Meikai University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2009
• 资助国家: 日本
• 起止时间: 2009 至 2011
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-21592371/
• 关键词: シグナル伝達; M2マクロファージ; 腫瘍; Il-4; マクロファージ; STAT6; IL-4; 免疫組織; CD163; 口腔扁平上皮癌; 遺伝子発現; 抗炎症; IL-13; 低酸素

Macrophages(Mφ) polarized with Th1 cytokines are called M1 Mφ, and are important for the clearance of pathogens and tumor cells. Mφactivated by Th2 cytokines IL4/IL-13 are classified as M2 Mφ, and are important in tissue repair and angiogenesis. We initially evaluated infiltrated Mφabout their phenotype by immunostainning in oral cancer tissue. We found that the infiltrated Mφhave an M2 phenotype. To further elucidate the mechanisms responsible for the M2-polarization of Mφin cancer, we examined the mechanisms of expression of the Arg-1 gene. Hypoxia further enhanced the IL-4/IL-13 induced Arg-1 mRNA expression. Although IL-4/IL-13-induced the Arg-1 expression has been shown to be dependent on STAT6 activation, hypoxia has no stimulatory effect on the STAT6-mediated transcriptional activation. These results suggest that hypoxia-mediated upregulation of the Arg-1 gene expression may result from cooperative interaction with different type of transcription factors and coactivators.

被Th 1细胞因子极化的巨噬细胞（Mφ）被称为M1 Mφ，并且对于病原体和肿瘤细胞的清除是重要的。由Th 2细胞因子IL 4/IL-13激活的Mφ被分类为M2 Mφ，并且在组织修复和血管生成中是重要的。我们通过免疫组化染色初步评估了口腔癌组织中浸润的Mφ的表型。我们发现浸润的Mφ具有M2表型。为了进一步阐明肿瘤中Mφ的M2极化机制，我们检测了Arg-1基因的表达机制。缺氧进一步增强IL-4/IL-13诱导的Arg-1 mRNA表达。虽然IL-4/IL-13诱导的Arg-1表达已被证明依赖于STAT 6的激活，但缺氧对STAT 6介导的转录激活没有刺激作用。这些结果表明，缺氧介导的Arg-1基因表达上调可能是由于不同类型的转录因子和共激活因子的协同作用。

项目成果

抗炎症性M2マクロファージにおけるArg-1遺伝子発現制御機構

抗炎M2巨噬细胞中Arg-1基因表达调控机制

• 发表时间: 2011
• 作者: 廣井美紀;大森喜弘
• 通讯作者: 大森喜弘

口腔扁平上皮癌における腫瘍関連M2マクロファージの局在

口腔鳞状细胞癌中肿瘤相关 M2 巨噬细胞的定位

• 发表时间: 2010
• 作者: Eguchi T.;et al.;森一将
• 通讯作者: 森一将

低酸素による抗炎症性M2マクロファージの遺伝子発現制御

缺氧对抗炎M2巨噬细胞基因表达的调节

• 发表时间: 2009
• 作者: Ohara-Nemoto Y;Shimoyama Y;Kimura Y;Kon A;Haraga H;Ono T;and Nemoto TK;廣井美紀
• 通讯作者: 廣井美紀