Effects of interleukins 2 and 12 on the levels of granzyme B and perforin and their mRNAs in tributyltin-exposed human natural killer cells.
Natural killer (NK) 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, and the preservation of wood. TBT can be found in edible items such as fish. A previous study showed that a 1 h exposure of NK cells to TBT caused persistent inhibition of NK-cell ability to destroy tumor cells in the 24 and 48 h periods following exposure and that this loss of function could be significantly prevented and/or reversed if the NK-stimulatory interleukins (IL) 2 or 12 were present during the 24 and 48 h periods. We had also shown that TBT exposure was able to significantly decrease the protein and mRNA levels of the cytotoxic proteins, granzyme B and perforin, and the phosphorylation of cAMP-response-element-binding protein (CREB) under these conditions. In this study we address the effects of IL-2 and IL-12 on the TBT-induced decreases in NK-cell levels of the cytotoxic proteins, their mRNAs, and CREB phosphorylation. IL-2 appeared to prevent/reverse TBT-induced declines in perforin protein levels and the mRNA for perforin seen in the 24 h period following a 1 h exposure to 300 nM TBT. However, the TBT-induced decreases in the levels of perforin and perforin mRNA seen in the 48 h period following a 1 h exposure to TBT were not statistically significantly prevented/reversed by IL-2. Additionally, the TBT-induced decreases in granzyme B, granzyme B mRNA, and CREB phosphorylation were not statistically significantly reversed by either IL-2 or IL-12 after 24 or 48 h.
Thomas
LeeShawn D
LD
Department of Biological Sciences, Tennessee State University, Nashville, TN 37209-1561, USA.
Shah
Hemangini
H
Bankhurst
Arthur D
AD
Whalen
Margaret M
MM
D000328:Adult; D002478:Cells, Cultured; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D053804:Granzymes; D006801:Humans; D018664:Interleukin-12 / Q000494:pharmacology*; D007376:Interleukin-2 / Q000494:pharmacology*; D020014:K562 Cells; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D012333:RNA, Messenger / Q000378:metabolism; D012697:Serine Endopeptidases / Q000235:genetics / Q000378:metabolism; D014220:Trialkyltin Compounds / Q000633:toxicity*
D007376:Interleukin-2; D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D012333:RNA, Messenger; D014220:Trialkyltin Compounds; D054353:Perforin; D018664:Interleukin-12; C011559:tributyltin; C509213:GZMB protein, human; D053804:Granzymes; D012697:Serine Endopeptidases