Document Detail

Tributyltin and dibutyltin alter secretion of tumor necrosis factor alpha from human natural killer cells and a mixture of T cells and natural killer cells.
MedLine Citation:
PMID:  23047847     Owner:  NLM     Status:  MEDLINE    
Butyltins (BTs) have been in widespread use. Tributyltin (TBT) has been used as a biocide in a variety of applications and is found in human blood samples. Dibutyltin (DBT) has been used as a stabilizer in polyvinyl chloride plastics and as a de-worming agent in poultry. DBT, like TBT, is found in human blood. Human natural killer (NK) cells are the earliest defense against tumors and viral infections and secrete the cytokine tumor necrosis factor-alpha (TNF-α). TNF-α is an important regulator of adaptive and innate immune responses. TNF-α promotes inflammation and an association between malignant transformation and inflammation has been established. Previously, we have shown that TBT and DBT were able to interfere with the ability of NK cells to lyse tumor target cells. Here we show that BTs alter cytokine secretion by NK cells as well as a mixture of T and NK lymphocytes (T/NK cells). We examined 24-, 48-h and 6-day exposures to TBT (200-2.5 nM) and DBT (5-0.05 μM) on TNF-α secretion by highly enriched human NK cells and T/NK cells. The results indicate that TBT (200-2.5 nM) decreased TNF-α secretion from NK cells. In the T/NK cells, 200 nM TBT decreased secretion whereas 100-5 nM TBT increased secretion of TNF-α. NK cells or T/NK cells exposed to higher concentrations of DBT showed decreased TNF-α secretion whereas lower concentrations showed increased secretion. The effects of BTs on TNF-α secretion are seen at concentrations present in human blood.
Kelsi Hurt; Tasia Hurd-Brown; Margaret Whalen
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Publication Detail:
Type:  In Vitro; Journal Article; Research Support, N.I.H., Extramural     Date:  2012-10-10
Journal Detail:
Title:  Journal of applied toxicology : JAT     Volume:  33     ISSN:  1099-1263     ISO Abbreviation:  J Appl Toxicol     Publication Date:  2013 Jun 
Date Detail:
Created Date:  2013-04-23     Completed Date:  2013-10-24     Revised Date:  2014-06-25    
Medline Journal Info:
Nlm Unique ID:  8109495     Medline TA:  J Appl Toxicol     Country:  England    
Other Details:
Languages:  eng     Pagination:  503-10     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 John Wiley & Sons, Ltd.
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MeSH Terms
Cell Survival / drug effects
Dose-Response Relationship, Drug
Killer Cells, Natural / drug effects,  metabolism*
Organotin Compounds / toxicity*
T-Lymphocytes / drug effects,  metabolism*
Trialkyltin Compounds / toxicity*
Tumor Necrosis Factor-alpha / metabolism*
Grant Support
1U54CA163066-01/CA/NCI NIH HHS; U54 CA163066/CA/NCI NIH HHS; U54 CA163069/CA/NCI NIH HHS; U54 CA163072/CA/NCI NIH HHS
Reg. No./Substance:
0/Organotin Compounds; 0/Trialkyltin Compounds; 0/Tumor Necrosis Factor-alpha; 1002-53-5/di-n-butyltin; 688-73-3/tributyltin

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