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Role of p44/42 activation in TBT‐ induced losses of granzyme B and perforin in human natural killer cells
Author(s) -
Abraha Abraham,
Whalen Margaret
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.862.1
Subject(s) - perforin , granzyme b , granzyme , microbiology and biotechnology , chemistry , cytotoxic t cell , biology , t cell , immunology , immune system , biochemistry , in vitro
Natural killer (NK) cells are key players in innate immunity and are responsible for early defense against tumors and viruses. It is well known that both perforin and granzyme B are released from NK cells upon target cell contact. The environmental pollutant, tributyltin chloride (TBT) has been reported to decrease human NK cell lytic function with accompanying activation of p44/42 and decreased levels of granzyme B and perforin. The current studies are designed to examine the role of the mitogen activated protein kinase (MAPK), p44/42, activation in TBT‐induced losses of granzyme B and perforin. p44/42 activation was blocked by the MEK inhibitor, PD98059. NK cells were exposed to PD98059 for 1 h followed by 1 h exposure to 200 or 100 nM TBT. Following the incubation period, NK cells were washed twice with media and incubated for 24 h period in compound‐free media. Western blot analysis using an antibody to granzyme B revealed that PD98059 was able to block 37% of the 200 nM TBT‐induced loss of granzyme B. Moreover, western blot analysis using an antibody to perforin revealed that PD98059 was able to block 42 % of the 200 nM TBT‐induced loss of perforin. Thus our data show a role for TBT‐induced activation of p44/42 in the decreases in granzyme B and perforin in NK cells and that the TBT‐induced p44/42 activation is not solely responsible for the losses of granzyme B and perforin protein levels.