Cell Biology and Toxicology

, Volume 26, Issue 5, pp 435–444 | Cite as

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

  • Fred D. Dudimah
  • Denisha Griffey
  • Xiaofei Wang
  • Margaret M. Whalen


Natural killer (NK) cells destroy (lyse) tumor cells, virally infected cells, and antibody-coated cells. Previous studies indicated that exposure to the environmental contaminant tributyltin (TBT) decreases the lytic function of NK cells and activates mitogen-activated protein kinases (MAPK), including p44/42 (Aluoch and Whalen Toxicology 209:263–277, 2005). If activation of p44/42 is required for TBT-induced decreases of lytic function, then activation of p44/42 to similar extents by pharmacological agents such as phorbol 12-myristate 13-acetate (PMA) should mimic to some extent changes induced in NK cells with TBT exposures. NK cells were exposed to PMA concentrations between 0.25 and 10 nM for 10 min, 1 h, and 6 h before determining the lytic function (51Cr release assay) and phosphorylation state of MAPKs (Western blot). A 1-h exposure of NK cells to 5 nM PMA resulted in a loss of lytic function of 47%. Western blot analysis showed that a 1-h exposure to 5 nM PMA caused a sixfold increase in phospho-p44/42 levels. Previous studies showed a fivefold increase in phospho-p44/42 in response to a 1-h exposure to 300 nM TBT. Exposure to 300 nM TBT caused about a 40% decrease in lytic function. This study supports the hypothesis that p44/42 activation (as seen with TBT exposures) can cause a loss of NK-cell lytic function.


MAPK p44/42 p38 PMA Anisomycin NK cells 



This research was supported by Grant 2S06GM-08092-34 from the National Institutes of Health.


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Copyright information

© Springer Science+Business Media B.V. 2010

Authors and Affiliations

  • Fred D. Dudimah
    • 1
  • Denisha Griffey
    • 2
  • Xiaofei Wang
    • 1
  • Margaret M. Whalen
    • 2
  1. 1.Department of Biological SciencesTennessee State UniversityNashvilleUSA
  2. 2.Department of ChemistryTennessee State UniversityNashvilleUSA

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