期刊
BIOLOGICAL & PHARMACEUTICAL BULLETIN
卷 37, 期 1, 页码 137-144出版社
PHARMACEUTICAL SOC JAPAN
DOI: 10.1248/bpb.b13-00659
关键词
tumor-associated macrophage; nuclear factor-kappaB; transfection; small interfering RNA
资金
- Ministry of Education, Culture, Sports, Science and Technology of Japan
- Programs for Promotion of Fundamental Studies in Health Sciences of the National Institute of Biomedical Innovation (NIBIO)
- Grants-in-Aid for Scientific Research [23240072, 23689003] Funding Source: KAKEN
Tumor-associated macrophages (TAMs) have an alternatively activated macrophage phenotype (M2) and promote cancer cell proliferation, angiogenesis and metastasis. Nuclear factor-kappaB (NF-kappa B) is one of the master regulators of macrophage polarization. Here, we investigated the effect of inhibition of NF-kappa B activity by small interfering RNA (siRNA) on the pro-tumor response of macrophages located in the tumor microenvironment in vitro. We used mouse peritoneal macrophages cultured in conditioned medium from colon-26 cancer cells as an in vitro TAM model (M2-like macrophages). Transfection of NF-kappa B (p50) siRNA into M2-like macrophages resulted in a significant decrease in the secretion of interleukin (IL)-10 (a T helper 2 (Th2) cytokine) and a significant increase of T helper 1 (Th1) cytokine production (IL-12, tumor necrosis factor-alpha, and IL-6). Furthermore, vascular endothelial growth factor production and matrix metalloproteinase-9 mRNA expression in M2-like macrophages were suppressed by inhibition of NF-kappa B expression with NF-kappa B (p50) siRNA. In addition, there was a reduction of arginase mRNA expression and increase in nitric oxide production. The cytokine secretion profiles of macrophages cultured in conditioned medium from either B16BL6 or PAN-02 cancer cells were also converted from M2 to classically activated (M1) macrophages by transfection of NF-kappa B (p50) siRNA. These results suggest that inhibition of NF-kappa B activity in M2-like macrophages alters their phenotype toward M1.
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