Activation of p44/42 MAPK plays a role in the TBT-induced loss of human natural killer (NK) cell function |
| |
Authors: | Fred D Dudimah Denisha Griffey Xiaofei Wang Margaret M Whalen |
| |
Institution: | (1) Department of Biological Sciences, Tennessee State University, Nashville, TN 37209, USA;(2) Department of Chemistry, Tennessee State University, 3500 John A. Merritt Blvd, Nashville, TN 37209, USA; |
| |
Abstract: | 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. |
| |
Keywords: | |
本文献已被 SpringerLink 等数据库收录! |
|