1. The p,p'-DDE disturbs the M1 function without affecting the M2 phenotype nor unstimulated bone marrow-derived macrophages from BALB/c mice.
- Author
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Cortés-Montoya V, Ortiz-Robles CD, Rivera-Maya OB, Palacios-Valladares JR, Ramirez-Gutierrez EF, and Calderón-Aranda ES
- Subjects
- Animals, Humans, Mice, Arginase genetics, Arginase metabolism, Arginase pharmacology, DDT metabolism, DDT pharmacology, Mice, Inbred BALB C, Phenotype, Reactive Oxygen Species metabolism, Tumor Necrosis Factor-alpha genetics, Dichlorodiphenyl Dichloroethylene toxicity, Dichlorodiphenyl Dichloroethylene metabolism, Macrophages drug effects, Macrophages metabolism
- Abstract
DDT, a persistent organic pollutant, remains affecting human health worldwide. DDT and its most persistent metabolite (p,p'-DDE) negatively affect the immune response regulation and mechanisms involved in protecting against pathogens Such metabolite decreases the capability to limit intracellular growth of Mycobacterium microti and yeast. However, the effect on unstimulated (M0) and anti-inflammatory macrophages (M2) has been evaluated scanty. Herein, we evaluated the impact of p,p'-DDE at environmentally relevant concentrations (0.125, 1.25, 2.5, and 5 µg/mL) on bone marrow-derived macrophages stimulated with IFNγ+LPS to M1 or with IL-4 +IL-13 to M2. Thus we study whether the p,p'-DDE induces M0 to a specific phenotype or modulates activation of the macrophage phenotypes and explains, at least partly, the reported effects of p,p'-DDE on the M1 function. The p,p'-DDE did not affect the cell viability of M0 or the macrophage phenotypes. In M1, the p,p'-DDE decreased NO•- production and IL-1β secretion, but increasing cellular ROS and mitochondrial O
2 •-, but did not alter iNOS, TNF-α, MHCII, and CD86 protein expression nor affect M2 markers arginase activity, TGF-β1, and CD206; p,p'-DDE, did not affect marker expression in M0 or M2, supporting that its effects on M1 parameters are not dependent on M0 nor M2 modulation. The decreasing of NO•- production by the p,p'-DDE without altering iNOS levels, Arginase activity, or TNF-α, but increasing cellular ROS and mitochondrial O2 suggests that p,p'-DDE interferes with the iNOS function but not with its transcription. The p,p'-DDE decreasing of IL-1β secretion, without any effect on TNF-α, suggest that an alteration of specific targets involved in IL-1β secretion may be affected and related to ROS induction. The p,p'-DDE effect on iNOS function and the IL-1β secretion process, as the NLRP3 activation, deserves further study., Competing Interests: 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., (Copyright © 2023 Elsevier B.V. All rights reserved.)- Published
- 2023
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