|
KMID : 0939920140460030297
|
|
대한암학회지
2014 Volume.46 No. 3 p.297 ~ p.306
|
|
|
Interleukin-17 Indirectly Promotes M2 Macrophage Differentiation through Stimulation of COX-2/PGE2 Pathway in the Cancer Cells
|
|
Li Qingli
Liu Lunxu
Zhang Qiuyang
Liu Sen
Ge Dongxia
You Zongbing
|
|
|
Abstract
|
|
|
Purpose: Interleukin-17 (IL-17) is a proinflammatory cytokine that plays important roles in inflammation, autoimmunity, and cancer. The purpose of this study was to determine if IL-17 indirectly regulates macrophage differentiation through up-regulation of cyclooxygenase-2 (COX-2) expression in the cancer cell lines.
Materials and Methods: Human cervical cancer HeLa, human lung cancer A549, and mouse prostate cancer Myc-CaP/CR cell lines were treated with recombinant IL-17; Western blot analysis, enzyme-linked immunosorbent assay, and quantitative real-time polymerase chain reaction analysis were utilized to examine the cellular responses.
Results: IL-17 up-regulated expression of COX-2 mRNA and protein in HeLa, A549, and Myc- CaP/CR cell lines. IL-17’s effects were mediated through nuclear factor-κB and ERK1/2 signaling pathways as the inhibitors of these pathways could inhibit IL-17- induced COX-2 expression. The conditional medium obtained from the cancer cells contained prostaglandin E2, the levels of which were increased by IL-17 treatment. When treated with the conditional medium, particularly with the IL-17-induced conditional medium, mouse RAW264.7 macrophages and human THP-1 monocytes expressed higher levels of IL-10 (a marker of M2 macrophages) than inducible nitric oxide synthase or tumor necrosis factor α (markers of M1 macrophages). In contrast, when RAW264.7 and THP-1 cells were treated directly with IL-17, expression of these marker genes was not markedly changed.
Conclusion: The results of this study suggest that IL-17 indirectly promotes M2 macrophage differentiation through stimulation of the COX-2/PGE2 pathway in the cancer cells, thus IL-17 plays an indirect role in regulating the tumor immune microenvironment.
|
|
|
KEYWORD
|
|
|
Interleukin-17, Cyclooxygenase-2, Dinoprostone, Neoplasms, Macrophages, Tumor microenvironment
|
|
|
FullTexts / Linksout information
|
|
|
|
|
Listed journal information
|
|
    
|
|