PMID- 31046488 OWN - NLM STAT- MEDLINE DCOM- 20191202 LR - 20191202 IS - 1532-2513 (Electronic) IS - 0892-3973 (Linking) VI - 41 IP - 2 DP - 2019 Apr TI - A comparative evaluation of the immunotoxicity and immunomodulatory effects on macrophages exposed to aromatic trihalogenated DBPs. PG - 319-326 LID - 10.1080/08923973.2019.1608444 [doi] AB - Objective: 2,4,6-trichlorophenol (TCP), 2,4,6-tribromophenol (TBP), and 2,4,6-triiodophenol (TIP) are three aromatic halogenated disinfection byproducts (DBPs) identified in chlorinated saline effluents. This study aimed to evaluate and compare their immunotoxicity and immunomodulatory effects on macrophages. Materials and methods: CCK-8 assay was used to evaluate cytotoxicity of TCP, TBP, and TIP in mouse macrophage RAW264.7 cells. A light microscope and digital camera were used to record the morphological changes of RAW264.7 cells. qRT-PCR was used to measure the mRNA levels of polarization markers and secreted cytokines. Cytokine production was also detected by ELISA. Flow cytometry was performed to analyze the expression of M1 and M2 markers on macrophages. Results: TCP, TBP, and TIP had different cytotoxic effects on macrophages. The rank order of cytotoxicity was TIP > TBP > TCP. Furthermore, the three halogenated DBPs displayed different preferences for macrophage polarization. Intriguingly, 200 muM TIP remarkably induced the M2-dominant polarization of macrophages, while 200 muM TCP induced an M1-dominant polarization of macrophages. TBP has a moderate ability in inducing M1 and M2 polarization compared with TCP and TIP. Conclusions: TIP displayed higher cytotoxicity against macrophages than TBP and TCP, its brominated and chlorinated analogs. Since M1 and M2 macrophages facilitate the inflammatory and anti-inflammatory responses, respectively, the discrepancy of TCP, TBP, and TIP in inducing macrophage polarization may lead to distinct immunomodulatory and toxicological outcomes, thus giving rise to different types of diseases. This finding may provide novel insights into evaluating the toxicity of environmental pollutants on the immune system. FAU - Xie, Yanci AU - Xie Y AD - a Department of Pathogen Biology, Key Laboratory of Pathogen Biology of Jiangsu Province , Nanjing Medical University , Nanjing , China. FAU - Jiang, Liujing AU - Jiang L AD - b School of the Environment, State Key Laboratory of Pollution Control and Resource Reuse , Nanjing University , Nanjing , China. FAU - Qiu, Jingfan AU - Qiu J AD - a Department of Pathogen Biology, Key Laboratory of Pathogen Biology of Jiangsu Province , Nanjing Medical University , Nanjing , China. FAU - Wang, Yong AU - Wang Y AD - a Department of Pathogen Biology, Key Laboratory of Pathogen Biology of Jiangsu Province , Nanjing Medical University , Nanjing , China. AD - c School of Public Health, Key Laboratory of Infectious Diseases , Nanjing Medical University , Nanjing , China. LA - eng PT - Comparative Study PT - Journal Article DEP - 20190503 PL - England TA - Immunopharmacol Immunotoxicol JT - Immunopharmacology and immunotoxicology JID - 8800150 RN - 0 (Chlorophenols) RN - 0 (Immunologic Factors) RN - 0 (Phenols) RN - 9RB2R81A7U (2,4,6-triiodophenol) RN - MHS8C5BAUZ (2,4,6-trichlorophenol) RN - YS6K3EU393 (2,4,6-tribromophenol) SB - IM MH - Animals MH - Chlorophenols/*toxicity MH - Drug Evaluation MH - Immunologic Factors/*toxicity MH - Macrophages/*immunology/pathology MH - Mice MH - Phenols/*toxicity MH - RAW 264.7 Cells OTO - NOTNLM OT - Halogenated disinfection byproducts OT - anti-inflammatory OT - inflammatory OT - macrophage OT - polarization EDAT- 2019/05/03 06:00 MHDA- 2019/12/04 06:00 CRDT- 2019/05/04 06:00 PHST- 2019/05/03 06:00 [pubmed] PHST- 2019/12/04 06:00 [medline] PHST- 2019/05/04 06:00 [entrez] AID - 10.1080/08923973.2019.1608444 [doi] PST - ppublish SO - Immunopharmacol Immunotoxicol. 2019 Apr;41(2):319-326. doi: 10.1080/08923973.2019.1608444. Epub 2019 May 3.