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Exposures to the environmental contaminants pentachlorophenol and dichlorodiphenyltrichloroethane increase production of the proinflammatory cytokine, interleukin‐1β, in human immune cells
Author(s) -
Martin Tamara J.,
Maise JaQuel,
Gabure Sahra,
Whalen Margaret M.
Publication year - 2019
Publication title -
journal of applied toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.784
H-Index - 87
eISSN - 1099-1263
pISSN - 0260-437X
DOI - 10.1002/jat.3798
Subject(s) - pentachlorophenol , proinflammatory cytokine , cytokine , immune system , secretion , chemistry , p38 mitogen activated protein kinases , interleukin , endocrinology , protein kinase a , biology , medicine , kinase , immunology , biochemistry , inflammation , environmental chemistry
Pentachlorophenol (PCP) and dichlorodiphenyltrichloroethane (DDT) are organochlorine environmental contaminants found in human blood at very significant levels (as high as 5 μ m for PCP and 260 n m for DDT). Cancers of the blood (lymphoma and myeloma) and kidney as well as others have been associated with exposure to these contaminants. Interleukin (IL)‐1β is a proinflammatory cytokine and is involved in stimulating cell proliferation. High levels of IL‐1β are associated with inflammatory diseases and tumor progression. Previous studies showed that PCP and DDT at certain concentrations were able to stimulate secretion of IL‐1β. This study shows that the increased secretion of IL‐1β seen with both contaminants is due to compound‐induced increases in the production of this cytokine. Increased production began within 6 hours of exposure to PCP and continued to increase up to 24 hours. DDT‐induced stimulation of IL‐1β appeared to be maximal after 6 hours of exposure and then diminished by 24 hours. The increases seen in IL‐1β production stimulated by PCP appear to be at least partially due to compound‐induced increases in IL‐1β mRNA. Although DDT caused increased production of IL‐1β, it did not appear to cause consistent increases in its mRNA. PCP‐ and DDT‐induced increases in IL‐1β production were dependent primarily on the p38 mitogen‐activated protein kinase pathway. These results indicate that both PCP and DDT are able to increase IL‐1β production in a p38 mitogen‐activated protein kinase‐dependent manner, which may have the potential to influence chronic inflammation.