Roles of mitogen-activated protein kinase pathways during Escherichia coli-induced apoptosis in U937 cells |
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Authors: | J. H. Wang Y. J. Zhou P. He B. Y. Chen |
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Affiliation: | (1) Department of Geriatrics, The Second Affiliated Hospital, China Medical University, Shenyang, P.R. China;(2) Department of Endocrinology and Metabolism, The Fourth Affiliated Hospital, China Medical University, Shenyang, P.R. China;(3) Department of Infectious Diseases, The First Affiliated Hospital, China Medical University, North 2nd Road 92, Heping Ward, Shenyang, 110001, P.R. China |
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Abstract: | Escherichia coli (E. coli) infections play an important and growing role in the clinic. In the present study, we investigated the involvement of members of the mitogen-activated protein kinase (MAPK) superfamily, including extracellular signal-regulated kinase (ERK), c-Jun NH2-terminal kinase (JNK) and p38 MAPK, and caspase-3 and 9 activity in E. coli-induced apoptosis in human U937 cells. We found that E. coli induces apoptosis in U937 cell lines in a dose- and time-dependent manner, p38 MAPK and JNK were activated after 10 min of infection with E. coli. In contrast, ERK1/2 was down-regulated in a time-dependent manner. The levels of total (phosphorylation state-independent) p38 MAPK, JNK and ERK1/2 did not change in E. coli-infected U937 cells at all times examined. Moreover, exposure of U937 cells to E. coli led to caspase-3 and 9 activity. For the evaluation of the role of MAPKs, PD98059, SB203580 and SP600125 were used as MAPKs inhibitors for ERK1/2, p38 MAPK and JNK. Inhibition of ERK1/2 with PD98059 caused further enhancement in apoptosis and caspase-3 and 9 activity, while a selective p38 MAPK inhibitor, SB203580 and JNK inhibitor, SP600125 significantly inhibited E. coli-induced apoptosis and caspase-3 and 9 activity in U937 cells. The results were further confirmed by the observation that the caspase inhibitors Z-DEVD-FMK and Z-LEHD-FMK blocked E. coli-induced U937 apoptosis. Taken together, we have shown that E. coli increase p38 MAPK and JNK and decrease ERK1/2 phosphorylation and increase caspase-3 and 9 activity in U937 cells. |
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Keywords: | E. coli Apoptosis ERK JNK p38 MAPK Caspase-3/9 |
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