Parny M., Bernad J., Prat M., Salon M., Aubouy Agnès, Bonnafe E., Coste A., Pipy B., Treilhou M. (2021). Comparative study of the effects of ziram and disulfiram on human monocyte-derived macrophage functions and polarization : involvement of zinc. Cell Biology and Toxicology, 37 (3), 379-400. ISSN 0742-2091.
Titre du document
Comparative study of the effects of ziram and disulfiram on human monocyte-derived macrophage functions and polarization : involvement of zinc
Année de publication
2021
Auteurs
Parny M., Bernad J., Prat M., Salon M., Aubouy Agnès, Bonnafe E., Coste A., Pipy B., Treilhou M.
Source
Cell Biology and Toxicology, 2021,
37 (3), 379-400 ISSN 0742-2091
Ziram, a zinc dithiocarbamate is widely used worldwide as a fungicide in agriculture. In order to investigate ziram-induced changes in macrophage functions and polarization, human monocytes-derived macrophages in culture were treated with ziram at 0.01-10 mu mol.L(-1)for 4-24 h. To characterize zinc involvement in these changes, we also determined the effects of disulfiram alone (dithiocarbamate without zinc) or in co-incubation with ZnSO4. We have shown that ziram and disulfiram at 0.01 mu mol.L(-1)increased zymosan phagocytosis. In contrast, ziram at 10 mu mol.L(-1)completely inhibited this phagocytic process, the oxidative burst triggered by zymosan and the production of TNF-alpha, IL-1 beta, IL-6, and CCL2 triggered by LPS. Disulfiram had the same effects on these macrophages functions only when combined with zinc (10 mu mol.L-1). In contrast, at 10 mu mol.L(-1)ziram and zinc associated-disulfiram induced expression of several antioxidants genes HMOX1, SOD2, and catalase, which could suggest the induction of oxidative stress. This oxidative stress could be involved in the increase in late apoptosis induced by ziram (10 mu mol.L-1) and zinc associated-disulfiram. Concerning gene expression profiles of membrane markers of macrophage polarization, ziram at 10 mu mol.L(-1)had two opposite effects. It inhibited the gene expression of M2 markers (CD36, CD163) in the same way as the disulfiram-zinc co-treatment. Conversely, ziram induced gene expression of other M2 markers CD209, CD11b, and CD16 in the same way as treatment with zinc alone. Disulfiram-zinc association had no significant effects on these markers. These results taken together show that ziram via zinc modulates macrophages to M2-like anti-inflammatory phenotype which is often associated with various diseases.
Plan de classement
Sciences fondamentales / Techniques d'analyse et de recherche [020]
;
Santé : généralités [050]
Localisation
Fonds IRD [F B010079402]
Identifiant IRD
fdi:010079402
