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

Catlin, ReEtta; Shah, Hemangini; Bankhurst, Arthur D.; Whalen, Margaret M.

doi:10.1016/j.etap.2005.03.012

Cited by 14 publications

(18 citation statements)

References 47 publications

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“…Levels of DBT in human blood have been found to range from undetectable to as high as 0.31 µM (Kannan et al, 1999; Whalen et al , 1999). Our previous studies have also shown that there is a loss of cell surface protein expression and of cytolytic proteins (granzyme B and perforin) that accompany this loss of lytic function (Odman-Ghazi et al 2003; Catlin et al, 2005). In this study we examine the effects of DBT exposures on several enzymes whose functions are key to regulating NK cell function, in an effort to elucidate the mechanism by which DBT causes NK cells to lose function.…”

Section: Discussionmentioning

confidence: 90%

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

et al. 2010

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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, appears 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.

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Section: Discussionmentioning

confidence: 90%

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

et al. 2010

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“…The predominant decrease in cell surface proteins were in CD16 and CD56 which are both important in the binding of NK cells to their targets (Mandelboim et al, 1999; Nitta et al, 1989). Decreases in cytolytic proteins and their mRNAs were also seen with both TBT and DBT (Thomas et al, 2004; Catlin et al, 2005). BT exposures have also been shown to cause a rapid activation of several MAPKs, most especially, p44/42 (Aluoch and Whalen, 2005; Aluoch et al, 2006; Aluoch et al, 2007; Odman-Ghazi, et al, 20101).…”

Section: Discussionmentioning

confidence: 94%

“…Both TBT and DBT significantly inhibit the lytic function of NK cells with accompanying loss of cell surface and cytolytic protein expression (Thomas et al, 2004; Catlin et al, 2005; Whalen et al , 2002b; Odman-Ghazi, 2003). The predominant decrease in cell surface proteins were in CD16 and CD56 which are both important in the binding of NK cells to their targets (Mandelboim et al, 1999; Nitta et al, 1989).…”

Section: Discussionmentioning

confidence: 99%

“…In previous studies examining the effects of BTs on NK cells we have found that BT exposures decrease the lytic function (Whalen et al, 1999; Whalen et al, 2002a; Dudimah et al, 2007a,b), binding function (Whalen et al , 2002b; Odman-Ghazi, 2003), lytic protein (granzyme and perforin) levels (Thomas et al, 2004; Catlin et al, 2005), and expression of certain cell surface proteins (Whalen et al , 2002b; Odman-Ghazi, 2003) in NK cells. We have also shown that exposure to BTs caused activation of mitogen activated protein kinases (MAPKs) in NK cells within 10 minutes of exposure (Aluoch and Whalen, 2005; Aluoch et al, 2006; Aluoch et al, 2007: Odman-Ghazi et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

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Effects of butyltin exposures on MAP kinase-dependent transcription regulators in human natural killer cells

Whalen

2010

Toxicology Mechanisms and Methods

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Natural Killer (NK) cells are a major immune defense mechanism against cancer development and viral infection. The butyltins (BTs), tributyltin (TBT) and dibutyltin (DBT) have been widely used in industrial and other applications and significantly contaminate the environment. Both TBT and DBT have been detected in human blood. These compounds inhibit the lytic and binding function of human NK cells and thus could increase the incidence of cancer and viral infections. Butyltin (BT)-induced loss of NK function is accompanied by activation of mitogen activated protein kinases (MAPKs) and decreases in expression of cell-surface and cytolytic proteins. MAPKs activate components of the transcription regulator AP-1 and activate the transcription regulator Elk-1. Based on the fact that BTs activate MAPKs and alter protein expression, the current study examined the effect of BT exposures on the levels and phosphorylation states of the components of AP-1 and the phosphorylation state of Elk-1. Exposure to 300 nM TBT for 10 min increased the phosphorylation of c-Jun in NK cells. 1 h exposures to 300 nM and 200 nM TBT increased the phosphorylation and overall level of c-Jun. During a 300 nM treatment with TBT for 1 h the binding activity of AP-1 was significantly decreased. There were no significant alterations of AP-1 components or of Elk-1 with DBT exposures. Thus, it appears that TBT-induced alterations on phosphorylation, total levels and binding activity of c-Jun might contribute to, but are not fully responsible for, TBT-induced alterations of NK protein expression.

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“…International Maritime Organization (IMO) prohibited the application of TBT in antifouling paints from 17th September 2008 [3]. Another butyltin -dibutyltin (DBT) is commonly used as heat and light stabilizer for PCV materials, to speed up the production of plastics, and as a deworming agent in poultry [4]. DBT is also known as a degradation product from tributyltin (TBT).…”

Section: Introductionmentioning

confidence: 99%