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

doi:10.1007/s10565-010-9157-3

Paper

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

Published Mar 24, 2010 · S. O. Odman-Ghazi, Abraham B Abraha, E. T. Isom

Cell Biology and Toxicology

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14

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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.

In Vitro Study

Study Snapshot

Dibutyltin exposure activates MAP kinases in human natural killer cells, potentially explaining its decreased ability to destroy tumor cells.

PopulationOlder adults (50-71 years)

Sample size24

MethodsObservational

OutcomesBody Mass Index projections

ResultsSocial networks mitigate obesity in older groups.

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Paper

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

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References

Activation of p44/42 MAPK plays a role in the TBT-induced loss of human natural killer (NK) cell function

Activation of p44/42 MAPK plays a role in the TBT-induced loss of human natural killer (NK) cell function, with pharmacological agents like PMA mimicking TBT exposures.

Effect Of Dibutyltin On ATP Levels In Human Natural Killer Cells

Dibutyltin exposure decreases ATP levels in NK cells, but tumor lysing function can be reduced independent of ATP levels, and the effects of DBT on ATP levels and tumor lysing function are irreversible.

Pattern of MAP kinases p44/42 and JNK activation by non-lethal doses of tributyltin in human natural killer cells

Tributyltin activates the anti-apoptotic p44/42 pathway more than the pro-apoptotic JNK pathway, potentially explaining how NK cell viability is maintained at non-lethal doses.

Alteration of an essential NK cell signaling pathway by low doses of tributyltin in human natural killer cells.

Low doses of tributyltin significantly decrease NK cell cytotoxic function and activate MAPKs, p38, and p44/42 within ten minutes of exposure, potentially increasing viral infections and tumor growth.

Dibutyltin exposure decreases granzyme B and perforin in human natural killer cells.

Dibutyltin exposure decreases granzyme B and perforin levels in human natural killer cells, potentially due to decreased transcription or increased mRNA degradation.

Citations

An IL-15 Superagonist, ALT-803, Enhances Antibody-Dependent Cell-Mediated Cytotoxicity Elicited by the Monoclonal Antibody NEO-201 Against Human Carcinoma Cells

ALT-803 enhances antibody-dependent cell-mediated cytotoxicity (ADCC) against human carcinoma cells by modulating natural killer (NK) activation and cytotoxicity, suggesting potential clinical use in combination with NEO-201 for human carcinoma treatment.

Dibutyltin depressed immune functions via NF‐κB, and JAK/STAT signaling pathways in zebrafish (Danio rerio)

Dibutyltin (DBT) suppresses immune functions in zebrafish by suppressing IKK/IkBa/NFkBp65 and JAK/STAT signaling pathways.

Activation of protein kinase C and protein kinase D in human natural killer cells: effects of tributyltin, dibutyltin, and tetrabromobisphenol A

Exposure of human NK cells to lysis sensitive tumor cells activates PKC and PKD, while exposure to environmental contaminants like tributyltin and dibutyltin does not significantly affect these enzymes.

Secretion of interferon gamma from human immune cells is altered by exposure to tributyltin and dibutyltin

Exposure to tributyltin and dibutyltin alters interferon gamma secretion from human immune cells, potentially impacting immune responses and influencing immune competence.

Hexabromocyclododecane and tetrabromobisphenol A alter secretion of interferon gamma (IFN-γ) from human immune cells

Exposure to HBCD and TBBPA may disrupt immune regulation mediated by IFN-, with the p44/42 (ERK1/2) MAPK pathway playing a key role in HBCD-induced increases in IFN- secretion.