PMID- 31026635 OWN - NLM STAT- MEDLINE DCOM- 20190607 LR - 20190607 IS - 1879-1026 (Electronic) IS - 0048-9697 (Linking) VI - 675 DP - 2019 Jul 20 TI - C(9-13) chlorinated paraffins cause immunomodulatory effects in adult C57BL/6 mice. PG - 110-121 LID - S0048-9697(19)31728-0 [pii] LID - 10.1016/j.scitotenv.2019.04.199 [doi] AB - Short-chain chlorinated paraffins (SCCPs, C(10-13)) were listed as persistent organic pollutants (POPs) by the Stockholm Convention in 2017 and pose extensive exposure risks to humans. To our knowledge, there have been no studies reporting the immmunomodulatory effects of SCCPs until now. C(9)-CPs have also been shown to be present in the environment. In this study, adult male C57BL/6 mice were exposed to 1, 10, or 100 mg/kg/d C(9-13)-CPs by gavage for 28 d. The results showed that compared to those of the controls, exposure to C(9-13)-CPs led to increased spleen weight, delimited germinal centers, enhanced energy metabolism, and elevated glutathione content, but no variation in the malonaldehyde level in the spleen was observed. Exposure to C(9-13)-CPs also increased the populations of splenic lymphocytes, T lymphocytes, NK cells, and the ratio of the CD3(+)/CD19(+) subsets and CD4(+)/CD8(+) subsets compared to those of the controls. RNA-seq revealed 424 differentially expressed genes (DEGs) (fold change >/= 1.5, FDR < 0.05) in the spleen between the control group and the 100 mg/kg/d C(9-13)-CPs-treated group. KEGG analysis demonstrated that folate biosynthesis, pathways in cancer and thyroid hormone signaling were the three most significantly enriched pathways, and despite not reaching statistical significance, some immune-related pathways were also enriched in the KEGG functional enrichment analysis, including the chemokine signaling pathway (FDR < 0.0584), the NF-kappaB signaling pathway (FDR < 0.0663), Th17 cell differentiation (FDR < 0.0839), and the Jak-STAT signaling pathway. Moreover, compared to those of the controls, exposure to C(9-13)-CPs enhanced the Concanavalin A (Con A)-stimulated cultured splenocyte proliferation, while the exposure showed no effect on the splenocyte proliferation that was stimulated by lipopolysaccharides (LPS). Taken together, these results demonstrated that subacute exposure to C(9-13)-CPs could have immunomodulatory effects in mice. The present study helps to provide an understanding of the comprehensive health risks posed by C(9-13)-CPs. CI - Copyright (c) 2019 Elsevier B.V. All rights reserved. FAU - Wang, Xia AU - Wang X AD - College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou 310014, China. FAU - Zhu, Jianbo AU - Zhu J AD - College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou 310014, China. FAU - Kong, Baida AU - Kong B AD - College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou 310014, China. FAU - He, Bingnan AU - He B AD - College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou 310014, China. FAU - Wei, Lai AU - Wei L AD - College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou 310014, China. FAU - Jin, Yuanxiang AU - Jin Y AD - College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou 310014, China. FAU - Shan, Yudong AU - Shan Y AD - College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou 310014, China. FAU - Wang, Weitao AU - Wang W AD - College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou 310014, China. FAU - Pan, Chunqiang AU - Pan C AD - College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou 310014, China. FAU - Fu, Zhengwei AU - Fu Z AD - College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou 310014, China. Electronic address: azwfu@zjut.edu.cn. LA - eng PT - Journal Article DEP - 20190416 PL - Netherlands TA - Sci Total Environ JT - The Science of the total environment JID - 0330500 RN - 0 (Environmental Pollutants) RN - 0 (Hydrocarbons, Chlorinated) RN - 8002-74-2 (Paraffin) SB - IM MH - Animals MH - Environmental Pollutants/*toxicity MH - Hydrocarbons, Chlorinated/toxicity MH - Immunomodulation/*drug effects MH - Mice MH - Mice, Inbred C57BL MH - Paraffin/*toxicity MH - *Toxicity Tests OTO - NOTNLM OT - C(9-13)-chlorinated paraffins OT - Immunomodulatory effects OT - Mice OT - Short-chain chlorinated paraffins OT - Transcriptomic analysis EDAT- 2019/04/27 06:00 MHDA- 2019/06/08 06:00 CRDT- 2019/04/27 06:00 PHST- 2018/12/29 00:00 [received] PHST- 2019/03/22 00:00 [revised] PHST- 2019/04/12 00:00 [accepted] PHST- 2019/04/27 06:00 [pubmed] PHST- 2019/06/08 06:00 [medline] PHST- 2019/04/27 06:00 [entrez] AID - S0048-9697(19)31728-0 [pii] AID - 10.1016/j.scitotenv.2019.04.199 [doi] PST - ppublish SO - Sci Total Environ. 2019 Jul 20;675:110-121. doi: 10.1016/j.scitotenv.2019.04.199. Epub 2019 Apr 16.