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Di-(2-ethylhexyl) phthalate enhances melanoma tumor growth via differential effect on M1-and M2-polarized macrophages in mouse model

Title
Di-(2-ethylhexyl) phthalate enhances melanoma tumor growth via differential effect on M1-and M2-polarized macrophages in mouse model
Author
계명찬
Keywords
Di-(2-ethylhexyl) phthalate (DEHP); Macrophage polarization; M1-type; M2-type; Endocrine disruptor; Tumor growth
Issue Date
2018-02
Publisher
ELSEVIER SCI LTD
Citation
ENVIRONMENTAL POLLUTION, v. 233, page. 833-843
Abstract
Phthalates are widely used as plasticizers that influence sexual and reproductive development. Here, we investigated whether di-(2-ethylhexyl) phthalate (DEHP) affects macrophage polarization that are associated with tumor initiation and progression. No changes were observed in LPS- or ConA-stimulated in vitro spleen B or T cell proliferation for 48 h, respectively. In contrast, macrophage functions were inhibited in response to DEHP for 12 h as judged by LPS-induced H2O2 and NO production and zymosan A-mediated phagocytosis. When six weeks old male mice were pre-exposed to 4.0 mg/kg DEHP for 21 days before the injection of B16F10 melanoma cells and post-exposed to 4.0 mg/kg DEHP for 7 days, tumor nodule formation and the changes in tumor volume were higher than those in control group. Furthermore, when male mice were intraperitoneally pretreated with DEHP for 3 or 4 weeks and peritoneal exudate cells (PECs) or bone marrow-derived macrophages (BMDMs) were incubated with lipopolysaccharide (LPS), the expression of COX-2, TNF-alpha, and IL-6 was reduced in DEHP-pretreated cells as compared with that in LPS-stimulated control cells. While the production of nitric oxide (NO) for 18 h was reduced by LPS-stimulated PECs and M1-type BMDMs, IL-4 expression was enhanced in LPS-stimulated BMDMs. When BMDMs were incubated with IL-4 for 30 h, arginase 1 for M2-type macrophages was increased in transcriptional and translational level. Data implicate that macrophages were differentially polarized by DEHP treatment, which reduced M1-polarzation but enhanced M2-polarization. Taken together, these data demonstrate that DEHP could affect in vivo immune responses of macrophages, leading to the suppression of their tumor-preventing ability. This suggests that individuals at high risk for tumor incidence should avoid long-term exposure to various kind of phthalate including DEHP.
URI
https://www.sciencedirect.com/science/article/pii/S0269749117321255?via%3Dihubhttp://repository.hanyang.ac.kr/handle/20.500.11754/117608
ISSN
0269-7491; 1873-6424
DOI
10.1016/j.envpol.2017.10.030
Appears in Collections:
COLLEGE OF NATURAL SCIENCES[S](자연과학대학) > LIFE SCIENCE(생명과학과) > Articles
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