The effects of tributyltin (TBT) on granzyme B and perforin protein and messenger RNA levels in human natural killer cells and their modulation by interleukins
Natural killer cells are a subset of lymphocytes that are capable of killing tumor cells, virally infected cells and antibody coated cells. Tributyltin (TBT) is a toxic chemical used for various industrial purposes such as: slime control in paper mills, disinfection of circulating industrial cooling waters, anti-fouling agents in shower curtains and the preservation of wood. TBT can be found in edible items such as dairy products and fish. This study investigates the mechanism by which TBT exposure decreases the immune function of human NK cells, in vitro. Cytotoxic function, the expression of the cytotoxic proteins (granzyme B and perforin), and cAMP response element binding protein (CREB) phosphorylation were examined. NK cells exposed to 300 nM TBT for 1h showed no consistent decrease in cytotoxic function, levels of granzyme B and perforin, or phosphorylation of CREB. However, mRNA levels for the cytotoxic proteins were decreased. A 24 h exposure to 200 nM TBT caused significant decreases in cytotoxic function, levels of granzyme B and perforin, and levels of granzyme B and perforin mRNA. When NK cells were exposed to 300 nM TBT followed by 24 or 48 h in TBT-free media, again there were decreases in cytotoxic function, levels of granzyme B and perforin and their mRNA. Additionally, both of these exposures showed significant decreases in phosphorylation of CREB. In this study we also address the effects of interleukins 2 and 12 on the TBT-induced decreases in NK-cell levels of the cytotoxic proteins and their mRNAs and CREB phosphorylation. A 1 h exposure to 300 nM TBT followed by 24 h in the presence of IL-2 or IL-12 caused a return of mRNA levels of granzyme B and perforin and IL-2 caused a return in perforin and granzyme B protein levels to baseline levels. IL-2 or IL-12, also prevented the TBT-induced decreases in the levels of granzyme B and perforin mRNA in the 48 h period following TBT exposure. These results indicate that IL-2 can return: granzyme B mRNA; perforin mRNA; perforin and granzyme B proteins; and phosphorylated CREB in TBT-exposed NK cells to levels seen in unexposed NK cells.
Anatomy & physiology|Animals|Immunology|Molecular biology|Cellular biology
LeeShawn D Thomas,
"The effects of tributyltin (TBT) on granzyme B and perforin protein and messenger RNA levels in human natural killer cells and their modulation by interleukins"
ETD Collection for Tennessee State University.