Dibutyltin activates MAP kinases in human natural killer cells, in vitro.

Abstract

Previous studies have shown that dibutyltin (DBT) interferes with the function of human natural killer (NK) cells, diminishing their capacity to destroy tumor cells, in vitro. DBT is a widespread environmental contaminant and has been found in human blood. As NK cells are our primary immune defense against tumor cells, it is important to understand the mechanism by which DBT interferes with their function. The current study examines the effects of DBT exposures on key enzymes in the signaling pathway that regulates NK responsiveness to tumor cells. These include several protein tyrosine kinases (PTKs), mitogen-activated protein kinases (MAPKs), and mitogen-activated protein kinase kinases (MAP2Ks). The results showed that in vitro exposures of NK cells to DBT had no effect on PTKs. However, exposures to DBT for as little as 10 min were able to increase the phosphorylation (activation) of the MAPKs. The DBT-induced activations of these MAPKs appear to be due to DBT-induced activations of the immediate upstream activators of the MAPKs, MAP2Ks. The results suggest that DBT-interference with the MAPK signaling pathway is a consequence of DBT exposures, which could account for DBT-induced decreases in NK function.

• Authors: Sabah O Odman-Ghazi, Abraham Abraha, Erica Taylor Isom, Margaret M Whalen
• Journal: Cell biology and toxicology (Cell Biol Toxicol) Vol. 26 Issue 5 Pg. 469-79 (Oct 2010) ISSN: 1573-6822 [Electronic] Netherlands
• PMID: 20333459 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Environmental Pollutants
• Organotin Compounds
• di-n-butyltin
• Protein-Tyrosine Kinases
• Mitogen-Activated Protein Kinases
• Mitogen-Activated Protein Kinase Kinases

Topics

• Blotting, Western
• Cell Survival (drug effects)
• Cells, Cultured
• Cytotoxicity, Immunologic (drug effects)
• Environmental Pollutants (toxicity)
• Female
• Humans
• Killer Cells, Natural (drug effects, enzymology, immunology)
• MAP Kinase Signaling System (drug effects)
• Male
• Mitogen-Activated Protein Kinase Kinases (metabolism)
• Mitogen-Activated Protein Kinases (metabolism)
• Organotin Compounds (toxicity)
• Phosphorylation (drug effects)
• Protein-Tyrosine Kinases (metabolism)