PMID- 29144988 OWN - NLM STAT- MEDLINE DCOM- 20180411 LR - 20210405 IS - 1873-6424 (Electronic) IS - 0269-7491 (Linking) VI - 233 DP - 2018 Feb TI - Di-(2-ethylhexyl) phthalate enhances melanoma tumor growth via differential effect on M1-and M2-polarized macrophages in mouse model. PG - 833-843 LID - S0269-7491(17)32125-5 [pii] LID - 10.1016/j.envpol.2017.10.030 [doi] AB - 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 H(2)O(2) 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. CI - Copyright (c) 2017 Elsevier Ltd. All rights reserved. FAU - Lee, Jae-Wook AU - Lee JW AD - Department of Bioscience and Biotechnology, Sejong University, Seoul 05006, Republic of Korea. FAU - Park, Sojin AU - Park S AD - Department of Bioscience and Biotechnology, Sejong University, Seoul 05006, Republic of Korea. FAU - Han, Hae-Kyoung AU - Han HK AD - Department of Bioscience and Biotechnology, Sejong University, Seoul 05006, Republic of Korea. FAU - Gye, Myung Chan AU - Gye MC AD - Department of Life Science, Institute for Natural Sciences, Hanyang University, Seoul 04763, Republic of Korea. Electronic address: mcgye@hanyang.ac.kr. FAU - Moon, Eun-Yi AU - Moon EY AD - Department of Bioscience and Biotechnology, Sejong University, Seoul 05006, Republic of Korea. Electronic address: eunyimoon@sejong.ac.kr. LA - eng PT - Journal Article DEP - 20171114 PL - England TA - Environ Pollut JT - Environmental pollution (Barking, Essex : 1987) JID - 8804476 RN - 0 (Interleukin-6) RN - 0 (Lipopolysaccharides) RN - 0 (Plasticizers) RN - 0 (Tumor Necrosis Factor-alpha) RN - 31C4KY9ESH (Nitric Oxide) RN - C42K0PH13C (Diethylhexyl Phthalate) RN - EC 3.5.3.1 (ARG1 protein, human) RN - EC 3.5.3.1 (Arginase) SB - IM MH - Animals MH - Arginase MH - Cell Proliferation/drug effects MH - Diethylhexyl Phthalate/*toxicity MH - Interleukin-6/metabolism MH - Lipopolysaccharides MH - Macrophages/*drug effects/metabolism/physiology MH - Male MH - Melanoma MH - Mice MH - Nitric Oxide/metabolism MH - Phagocytosis/drug effects MH - Plasticizers MH - Spleen/metabolism MH - Tumor Necrosis Factor-alpha/metabolism OTO - NOTNLM OT - Di-(2-ethylhexyl) phthalate (DEHP) OT - Endocrine disruptor OT - M1-type OT - M2-type OT - Macrophage polarization OT - Tumor growth EDAT- 2017/11/18 06:00 MHDA- 2018/04/12 06:00 CRDT- 2017/11/18 06:00 PHST- 2017/05/21 00:00 [received] PHST- 2017/10/08 00:00 [revised] PHST- 2017/10/08 00:00 [accepted] PHST- 2017/11/18 06:00 [pubmed] PHST- 2018/04/12 06:00 [medline] PHST- 2017/11/18 06:00 [entrez] AID - S0269-7491(17)32125-5 [pii] AID - 10.1016/j.envpol.2017.10.030 [doi] PST - ppublish SO - Environ Pollut. 2018 Feb;233:833-843. doi: 10.1016/j.envpol.2017.10.030. Epub 2017 Nov 14.