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J Appl Toxicol. 2017 Feb;37(2):181-191. doi: 10.1002/jat.3339. Epub 2016 May 17.

Dibutyltin-induced alterations of interleukin 1beta secretion from human immune cells.

Author information

1
Department of Biological Sciences, Tennessee State University, Nashville, TN, USA.
2
Department of Chemistry, Tennessee State University, Nashville, TN, USA.

Abstract

Dibutyltin (DBT) is used to stabilize polyvinyl chloride plastics (including pipes that distribute drinking water) and as a de-worming agent in poultry. DBT is found in human blood, and DBT exposures alter the secretion of tumor necrosis factor alpha and interferon gamma from lymphocytes. Interleukin (IL)-1β is a proinflammatory cytokine that regulates cellular growth, tissue restoration and immune response regulation. IL-1β plays a role in increasing invasiveness of certain tumors. This study reveals that exposures to DBT (24 h, 48 h and 6 days) modify the secretion of IL-1β from increasingly reconstituted preparations of human immune cells (highly enriched human natural killer cells, monocyte-depleted [MD] peripheral blood mononuclear cells [PBMCs], PBMCs, granulocytes and a preparation combining both PBMCs and granulocytes). DBT altered IL-1β secretion from all cell preparations. Higher concentrations of DBT (5 and 2.5 μm) decreased the secretion of IL-1β, while lower concentrations of DBT (0.1 and 0.05 μm) increased the secretion of IL-1β. Selected signaling pathways were examined in MD-PBMCs to determine if they play a role in DBT-induced elevations of IL-1β secretion. Pathways examined were IL-1β converting enzyme (caspase 1), mitogen-activated protein kinases and nuclear factor kappa B. Caspase 1 and mitogen-activated protein kinase pathways appear to be utilized by DBT in increasing IL-1β secretion. These results indicate that DBT alters IL-1β secretion from human immune cells in an ex. vivo system utilizing several IL-1β regulating signaling pathways. Thus, DBT may have the potential to alter IL-1β secretion in an in vivo system.

KEYWORDS:

MD-PBMCs; NK cells; PBMCs; dibutyltin; granulocytes; interleukin 1 beta

PMID:
27185338
PMCID:
PMC5114172
DOI:
10.1002/jat.3339
[Indexed for MEDLINE]
Free PMC Article

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