Brominated flame retardants, tetrabromobisphenol A and hexabromocyclododecane, activate mitogen-activated protein kinases (MAPKs) in human natural killer cells

Anita Cato, Lindsay Celada, Esther Caroline Kibakaya, Nadia Simmons, Margaret M. Whalen

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Natural killer (NK) cells provide a vital surveillance against virally infected cells, tumor cells, and antibody-coated cells through the release of cytolytic mediators and gamma interferon (IFN-γ). Hexabromocyclododecane (HBCD) is a brominated flame retardant used primarily in expanded (EPS) and extruded (XPS) polystyrene foams for thermal insulation in the building and construction industry. Tetrabromobisphenol A (TBBPA) is used both as a reactive and an additive flame retardant in a variety of materials. HBCD and TBBPA contaminate the environment and are found in human blood samples. In previous studies, we have shown that other environmental contaminants, such as the dibutyltin (DBT) and tributyltin (TBT), decrease NK lytic function by activating mitogen-activated protein kinases (MAPKs) in the NK cells. HBCD and TBBPA also interfere with NK cell(s) lytic function. The current study evaluates whether HBCD and/or TBBPA have the capacity to activate MAPKs and MAPK kinases (MAP2Ks). The effects of concentrations of HBCD and TBBPA that inhibited lytic function on the phosphorylation state and total levels of the MAPKs (p44/42, p38, and JNK) and the phosphorylation and total levels of the MAP2Ks (MEK1/2 and MKK3/6) were examined. Results indicate that exposure of human NK cells to 10–0.5 μM HBCD or TBBPA activate MAPKs and MAP2Ks. This HBCD and TBBPA-induced activation of MAPKs may leave them unavailable for activation by virally infected or tumor target cells and thus contributes to the observed decreases in lytic function seen in NK cells exposed to HBCD and TBBPA.

Original languageEnglish (US)
Pages (from-to)345-360
Number of pages16
JournalCell Biology and Toxicology
Volume30
Issue number6
DOIs
StatePublished - Nov 27 2014
Externally publishedYes

Fingerprint

Flame Retardants
Mitogen-Activated Protein Kinases
Natural Killer Cells
Construction Industry
Phosphorylation
Tumors
Chemical activation
Neoplasm Antibodies
MAP Kinase Kinase Kinases
tetrabromobisphenol A
hexabromocyclododecane
Polystyrenes
Thermal insulation
Construction industry
Interferon-gamma
Foams
Blood
X ray photoelectron spectroscopy
Hot Temperature
Cells

Keywords

  • Hexabromocyclododecane
  • MAP2K
  • MAP3K
  • MAPK
  • NK cells
  • Tetrabromobisphenol A

ASJC Scopus subject areas

  • Toxicology
  • Cell Biology
  • Health, Toxicology and Mutagenesis

Cite this

Brominated flame retardants, tetrabromobisphenol A and hexabromocyclododecane, activate mitogen-activated protein kinases (MAPKs) in human natural killer cells. / Cato, Anita; Celada, Lindsay; Kibakaya, Esther Caroline; Simmons, Nadia; Whalen, Margaret M.

In: Cell Biology and Toxicology, Vol. 30, No. 6, 27.11.2014, p. 345-360.

Research output: Contribution to journalArticle

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abstract = "Natural killer (NK) cells provide a vital surveillance against virally infected cells, tumor cells, and antibody-coated cells through the release of cytolytic mediators and gamma interferon (IFN-γ). Hexabromocyclododecane (HBCD) is a brominated flame retardant used primarily in expanded (EPS) and extruded (XPS) polystyrene foams for thermal insulation in the building and construction industry. Tetrabromobisphenol A (TBBPA) is used both as a reactive and an additive flame retardant in a variety of materials. HBCD and TBBPA contaminate the environment and are found in human blood samples. In previous studies, we have shown that other environmental contaminants, such as the dibutyltin (DBT) and tributyltin (TBT), decrease NK lytic function by activating mitogen-activated protein kinases (MAPKs) in the NK cells. HBCD and TBBPA also interfere with NK cell(s) lytic function. The current study evaluates whether HBCD and/or TBBPA have the capacity to activate MAPKs and MAPK kinases (MAP2Ks). The effects of concentrations of HBCD and TBBPA that inhibited lytic function on the phosphorylation state and total levels of the MAPKs (p44/42, p38, and JNK) and the phosphorylation and total levels of the MAP2Ks (MEK1/2 and MKK3/6) were examined. Results indicate that exposure of human NK cells to 10–0.5 μM HBCD or TBBPA activate MAPKs and MAP2Ks. This HBCD and TBBPA-induced activation of MAPKs may leave them unavailable for activation by virally infected or tumor target cells and thus contributes to the observed decreases in lytic function seen in NK cells exposed to HBCD and TBBPA.",
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AU - Celada, Lindsay

AU - Kibakaya, Esther Caroline

AU - Simmons, Nadia

AU - Whalen, Margaret M.

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