| 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
|
|
WOS Category
|
PHARMACOLOGY & PHARMACY
|
| Resource |
| Human and Animal Cells |
Colon-26(RCB2657)
B16/BL6(RCB2638) |
