Regulatory mechanisms of gene expression in anti-inflammatory M2 macrophages

巨噬细胞(Mφ)被Th1型细胞因子极化，称为M1 Mφ，对清除病原体和肿瘤细胞具有重要作用。由Th2型细胞因子IL-4/IL-13激活的M-φ被归类为M2-M-φ，在组织修复和血管生成中起重要作用。我们通过免疫组织化学染色初步评估了浸润性M-φ在口腔癌组织中的表型。我们发现浸润性M-φ具有M2表型。为了进一步阐明癌症中MφM2极化的机制，我们检测了Arg-1基因的表达机制。低氧进一步增强IL-4/IL-13诱导的Arg-1mRNA表达。虽然IL-4/IL-13诱导的Arg-1的表达依赖于STAT6的激活，但低氧对STAT6介导的转录激活没有刺激作用。这些结果表明，低氧介导的Arg-1基因表达上调可能是与不同类型的转录因子和共激活因子协同作用的结果。

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.