当前位置： SCI文献检索 > ARCHIVES OF ENVIRONMENTAL CONTAMINATION AND TOXICOLOGY期刊下所有文献 > Role of protein kinase C in TBT-induced inhibition of lytic function and MAPK activation in human natural killer cells.

Role of protein kinase C in TBT-induced inhibition of lytic function and MAPK activation in human natural killer cells.

Abstract：

:Human natural killer (NK) cells are lymphocytes that destroy tumor and virally infected cells. Previous studies have shown that exposure of NK cells to tributyltin (TBT) greatly diminishes their ability to destroy tumor cells (lytic function) while activating mitogen-activated protein kinases (MAPK) (p44/42, p38, and JNK) in NK cells. The signaling pathway that regulates NK lytic function appears to include activation of protein kinase C(PKC) as well as MAPK activity. TBT-induced activation of MAPKs would trigger a portion of the NK lytic signaling pathway, which would then leave the NK cell unable to trigger this pathway in response to a subsequent encounter with a target cell. In the present study we evaluated the involvement of PKC in inhibition of NK lysis of tumor cells and activation of MAPKs caused by TBT exposure. TBT caused a 2–3-fold activation of PKC at concentrations ranging from 50 to 300 nM (16–98 ng/ml),indicating that activation of PKC occurs in response to TBT exposure. This would then leave the NK cell unable to respond to targets. Treatment with the PKC inhibitor, bisindolylmaleimide I, caused an 85% decrease in the ability of NK cells to lyse tumor cells, validating the involvement of PKC in the lytic signaling pathway. The role of PKC in the activation of MAPKs by TBT was also investigated using bisindolylmaleimide I. The results indicated that, in NK cells where PKC activation was blocked, there was no activation of the MAPK, p44/42 in response to TBT.However, TBT-induced activation of the MAPKs, p38 and JNK did not require PKC activation. These results indicate the pivotal role of PKC in the TBT-induced loss of NK lytic function including activation of p44/42 by TBT in NK cells.

journal_name

Arch Environ Contam Toxicol

journal_title

Archives of environmental contamination and toxicology

authors

Abraha AB,Rana K,Whalen MM

doi

10.1007/s00244-010-9520-7

subject

Has Abstract

pub_date

2010-11-01 00:00:00

pages

661-9

issue

4

eissn

0090-4341

issn

1432-0703

journal_volume

59

pub_type

杂志文章

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