Tributyltin exposure causes decreased granzyme B and perforin levels in human natural killer cells

Thomas, LeeShawn D; Shah, Hemangini; Green, Stephanie A; Bankhurst, Arthur D.; Whalen, Margaret M.

doi:10.1016/j.tox.2004.04.002

Cited by 34 publications

(35 citation statements)

References 46 publications

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“…Thus, the decreased binding of AP-1 seen after a 1 h exposure to TBT is consistent with fewer Jun-Fos homodimers causing decreased AP-1 binding to its element. As mentioned above NK cytolytic protein levels appear to be at least in part regulated by AP-1 (Zhou and Meadows, 2003; Hanson et al, 1993) and thus, the decrease in their expression with TBT exposures (Thomas et al, 2004) is consistent with the decreased AP-1 function noted in this study.…”

Section: Discussionsupporting

confidence: 88%

“…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: 92%

“…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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Section: Discussionsupporting

confidence: 88%

Section: Discussionmentioning

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

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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“…It affects the function of human natural killer (NK) lymphocytes (Smialowicz et al 1989; van Loveren 1990; Ghoneum 1990) including interference with the ability of human NK cells to bind and lyse target cells (Whalen et al 1999; Dudimah et al 2007; Whalen et al 2002; Thomas et al 2004). Additionally, it has been shown to alter the secretion of the pro-inflammatory cytokines interferon (IFN)-γ, tumor necrosis factor (TNF)-α, and interleukin (IL)-1β from human immune cells ex vivo (Hurt et al 2013; Lawrence et al 2015; Brown and Whalen 2015).…”

Section: Introductionmentioning

confidence: 99%

Tributyltin exposure alters cytokine levels in mouse serum

Lawrence

Pellom

Shanker

et al. 2016

Journal of Immunotoxicology

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Tributyltin (TBT), a toxic environmental contaminant, has been widely utilized for various industrial, agricultural and household purposes. Its usage has led to a global contamination and its bioaccumulation in aquatic organisms and terrestrial mammals. Previous studies suggest that TBT has debilitating effects on the overall immune function of animals, rendering them more vulnerable to diseases. TBT (at concentrations that have been detected in human blood) alters secretion of inflammatory cytokines from human lymphocytes ex vivo. Thus, it is important to determine if specified levels of TBT can alter levels of cytokines in an in vivo system. Mice were exposed to biologically relevant concentrations of TBT (200, 100 or 25 nM final concentrations). The quantitative determination of interferon (IFN)-γ, tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL2, IL5, IL7, IL12βp40, IL13, IL15, KC, MIP1β, MIP2 and RANTES was performed in mouse sera by MAGPIX analysis and Western blot. Results indicated alterations (both decreases and increases) in several cytokines. The pro-inflammatory cytokines IFNγ, TNFα, IL-1β, IL-2, IL5, IL12βp40, and IL-15 were altered as were the chemokines MIP-1 and RANTES and the anti-inflammatory cytokine IL-13. Increases in IFNγ and TNFα were seen in serum of mice exposed to TBT for less than 24 hr. IL1-β, IL-12βp40, IL-5 and IL-15 were also modulated in mouse serum depending on the specific experiment and the exposure concentration. IL-2 was consistently decreased in mouse serum when animals were exposed to TBT. There were also TBT-induced increases in MIP-1β, RANTES, and IL-13. These results from human and murine samples clearly suggest that TBT exposures modulate the secretion inflammatory cytokines.

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n‐Butylzinnverbindungen [MAK Value Documentation in German language, 2008]

2012

The MAK‐Collection for Occupational Health and Safety

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Veröffentlicht in der Reihe Gesundheitsschädliche Arbeitsstoffe , 44. Lieferung, Ausgabe 2008 Der Artikel enthält folgende Kapitel: Allgemeiner Wirkungscharakter Wirkungsmechanismus Toxikokinetik und Metabolismus Aufnahme, Verteilung, Ausscheidung Metabolismus Erfahrungen beim Menschen Einmalige Exposition Wiederholte Exposition Wirkung auf Haut und Schleimhäute Allergene Wirkung Tierexperimentelle Befunde und In‐vitro‐Untersuchungen Akute Toxizität Subakute, subchronische und chronische Toxizität Wirkung auf Haut und Schleimhäute Auge Allergene Wirkung Reproduktionstoxizität Genotoxizität Kanzerogenität Sonstige Wirkungen Bewertung

show abstract

Tributyltin exposure causes decreased granzyme B and perforin levels in human natural killer cells

Cited by 34 publications

References 46 publications

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

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

Tributyltin exposure alters cytokine levels in mouse serum

n‐Butylzinnverbindungen [MAK Value Documentation in German language, 2008]

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