RRC ID 44710
Author Kono Y, Kawakami S, Higuchi Y, Yamashita F, Hashida M.
Title In vitro evaluation of inhibitory effect of nuclear factor-kappaB activity by small interfering RNA on pro-tumor characteristics of M2-like macrophages.
Journal Biol Pharm Bull
Abstract Tumor-associated macrophages (TAMs) have an alternatively activated macrophage phenotype (M2) and promote cancer cell proliferation, angiogenesis and metastasis. Nuclear factor-kappaB (NF-κB) is one of the master regulators of macrophage polarization. Here, we investigated the effect of inhibition of NF-κB 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-κB (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-α, 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-κB expression with NF-κB (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-κB (p50) siRNA. These results suggest that inhibition of NF-κB activity in M2-like macrophages alters their phenotype toward M1.
Volume 37(1)
Pages 137-44
Published 2014-1-1
DOI 10.1248/bpb.b13-00659
PII DN/JST.JSTAGE/bpb/b13-00659
PMID 24141263
MeSH Animals Arginase / genetics Arginase / metabolism Cell Line, Tumor Colonic Neoplasms / genetics Colonic Neoplasms / metabolism* Cytokines / metabolism* Interleukins / metabolism Lipopolysaccharides Macrophage Activation Macrophages / metabolism* Macrophages, Peritoneal / metabolism* Matrix Metalloproteinase 9 / metabolism Mice NF-kappa B / antagonists & inhibitors* Neovascularization, Pathologic* Nitric Oxide / metabolism Phenotype RNA, Messenger / metabolism RNA, Small Interfering / metabolism* Signal Transduction Th1 Cells / metabolism Transfection Tumor Necrosis Factor-alpha / metabolism Vascular Endothelial Growth Factor A / metabolism
IF 1.863
Times Cited 22
Human and Animal Cells Colon-26(RCB2657) B16/BL6(RCB2638)