PMID- 32057836 OWN - NLM STAT- MEDLINE DCOM- 20210104 LR - 20210602 IS - 1879-3177 (Electronic) IS - 0887-2333 (Print) IS - 0887-2333 (Linking) VI - 65 DP - 2020 Jun TI - Alterations in macrophage phagocytosis and inflammatory tone following exposure to the organochlorine compounds oxychlordane and trans-nonachlor. PG - 104791 LID - S0887-2333(19)30785-4 [pii] LID - 10.1016/j.tiv.2020.104791 [doi] AB - The role of macrophages in the innate immune response cannot be underscored however recent studies have demonstrated that both resident and recruited macrophages have critical roles in the pathogenesis of metabolic dysfunction. Given the recent data implicating exposure to persistent organic pollutants (POPs) in the pathogenesis of metabolic diseases, the current study was designed to examine the effects of the highly implicated organochlorine (OC) compounds oxychlordane and trans-nonachlor on overall macrophage function. Murine J774A.1 macrophages were exposed to trans-nonachlor or oxychlordane (0 - 20 microM) for 24 hours then phagocytosis, reactive oxygen species (ROS) generation, mitochondrial membrane potential, caspase activities, pro-inflammatory cytokine production, and macrophage plasticity were assessed. Overall, exposure to oxychlordane significantly decreased macrophage phagocytosis while both OC compounds significantly increased ROS generation. Exposure to trans-nonachlor significantly increased secretion of tumor necrosis factor alpha (TNFalpha) and interleukin-6 whereas oxychlordane had a biphasic effect on TNFalpha secretion. However, both oxychlordane and trans-nonachlor decreased basal expression of the M1 pro-inflammatory marker cyclooxygenase 2. Taken together, these data indicate that exposure to these two OC compounds have both compound and concentration dependent effects on macrophage function which may alter both the innate immune response and impact metabolic function of key organs involved in metabolic diseases. CI - Copyright (c) 2020 Elsevier Ltd. All rights reserved. FAU - Young, Darian AU - Young D AD - Mississippi State University College of Veterinary Medicine, 240 Wise Center Drive, P.O. Box 6100, Mississippi State, MS 39762, USA. FAU - Worrell, Aren AU - Worrell A AD - Mississippi State University College of Veterinary Medicine, 240 Wise Center Drive, P.O. Box 6100, Mississippi State, MS 39762, USA. FAU - McDevitt, Erin AU - McDevitt E AD - Mississippi State University College of Veterinary Medicine, 240 Wise Center Drive, P.O. Box 6100, Mississippi State, MS 39762, USA. FAU - Henein, Lucie AU - Henein L AD - Mississippi State University College of Veterinary Medicine, 240 Wise Center Drive, P.O. Box 6100, Mississippi State, MS 39762, USA. FAU - Howell, George E 3rd AU - Howell GE 3rd AD - Mississippi State University College of Veterinary Medicine, 240 Wise Center Drive, P.O. Box 6100, Mississippi State, MS 39762, USA.. Electronic address: geh3@msstate.edu. LA - eng GR - R21 ES030786/ES/NIEHS NIH HHS/United States PT - Journal Article DEP - 20200210 PL - England TA - Toxicol In Vitro JT - Toxicology in vitro : an international journal published in association with BIBRA JID - 8712158 RN - 0 (Hydrocarbons, Chlorinated) RN - 0 (Insecticides) RN - 0 (Reactive Oxygen Species) RN - 12789-03-6 (Chlordan) RN - 27304-13-8 (oxychlordane) RN - 3734-49-4 (nonachlor) SB - IM MH - Animals MH - Cell Line MH - Chlordan/*analogs & derivatives/toxicity MH - Hydrocarbons, Chlorinated/*toxicity MH - Inflammation MH - Insecticides/*toxicity MH - Macrophages/*drug effects/physiology MH - Membrane Potential, Mitochondrial/drug effects MH - Mice MH - Oxidative Stress/drug effects MH - Phagocytosis/drug effects MH - Reactive Oxygen Species/metabolism PMC - PMC7152568 MID - NIHMS1565549 OTO - NOTNLM OT - Inflammation OT - Macrophage OT - Oxychlordane OT - Persistent organic pollutant OT - Phagocytosis OT - Trans-nonachlor COIS- Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2020/02/15 06:00 MHDA- 2021/01/05 06:00 PMCR- 2021/06/01 CRDT- 2020/02/15 06:00 PHST- 2019/10/15 00:00 [received] PHST- 2020/01/10 00:00 [revised] PHST- 2020/02/08 00:00 [accepted] PHST- 2020/02/15 06:00 [pubmed] PHST- 2021/01/05 06:00 [medline] PHST- 2020/02/15 06:00 [entrez] PHST- 2021/06/01 00:00 [pmc-release] AID - S0887-2333(19)30785-4 [pii] AID - 10.1016/j.tiv.2020.104791 [doi] PST - ppublish SO - Toxicol In Vitro. 2020 Jun;65:104791. doi: 10.1016/j.tiv.2020.104791. Epub 2020 Feb 10.