Effects of non-dioxin-like polychlorinated biphenyl congeners (PCB 101, PCB 153 and PCB 180) alone or mixed on J774A.1 macrophage cell line: modification of apoptotic pathway |
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Authors: | Ferrante M C Mattace Raso G Esposito E Bianco G Iacono A Clausi M T Amero P Santoro A Simeoli R Autore G Meli R |
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Affiliation: | a Department of Pathology and Animal Health, University of Naples “Federico II”, 80131 Naples, Italy b Department of Experimental Pharmacology, University of Naples “Federico II”, Via D. Montesano 49, 80131 Naples, Italy c Department of Clinical and Experimental Medicine and Pharmacology, School of Medicine, University of Messina, Messina, Italy d Department of Pharmaceutical Sciences, School of Pharmacy, University of Salerno, Fisciano (SA), Italy |
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Abstract: | Non-dioxin-like polychlorinated biphenyls (PCBs) are stable and lipophilic chemicals that persist in the environment and tend to bioaccumulate in the food chains. In the present study, we have investigated the effect of PCBs 101, 153, and 180 on macrophage J774A.1 by assessing cell viability and apoptotic cell death. We have combined morphological techniques and biochemical ones to establish the relevance of apoptosis in macrophage cell death induced by PCBs, alone or in combination. Treatment with the examined PCBs caused the loss of cell viability and accelerated apoptosis in a concentration-dependent manner. Moreover, a synergistic effect on cell death and apoptosis was evidenced for all PCBs at concentrations which were inactive alone. The apoptosis induced by PCBs involved the increase of caspase-3 activity. Also, Bcl-2 and Bax proteins were assessed to elucidate the apoptosis machinery induced in macrophage cultures by PCBs. Our results indicate that the increase in PCB-induced apoptosis correlates with a reduction in the expression of antiapoptotic Bcl-2 and an increase in the expression of proapoptotic Bax. Interestingly, concentrations of PCBs inactive by themselves induce apoptosis when PCBs are combined. In conclusion, our findings suggest that, although less toxic than dioxin like congeners, the examined non-dioxin-like PCBs are equally dangerous as immunotoxic pollutants, also considering their presence as mixtures at higher levels than dioxin-like PCBs in biotic and abiotic matrices. |
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Keywords: | PCBs, polychlorinated biphenyls DL, dioxin-like NDL, non-dioxin-like LPS, lipopolysaccharide PI, propidium iodide DAPI, 4&prime ,6-diamidine-2&prime -phenylindole dihydrochloride DMSO, dimethyl sulphoxide FBS, foetal bovine serum MTT, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide OD, optical density PBS, phosphate buffered saline GAPDH, glyceraldehyde 3-phosphate dehydrogenase SEM, standard error mean |
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