PMID- 20600795 OWN - NLM STAT- MEDLINE DCOM- 20101112 LR - 20100810 IS - 1096-1208 (Electronic) IS - 0882-4010 (Linking) VI - 49 IP - 5 DP - 2010 Nov TI - Staphylococcus aureus induces apoptosis of human monocytic U937 cells via NF-kappaB signaling pathways. PG - 252-9 LID - 10.1016/j.micpath.2010.06.007 [doi] AB - Staphylococcus aureus (S. aureus) is an opportunistic pathogen and the major causative agent of numerous infections. S. aureus have been shown to induce apoptosis in many cell types. However, the mechanisms regulating primary monocytes and human monocytic U937 cell death following S. aureus challenge are unknown. In this study, we found that infection of primary monocytes and human monocytic U937 cells with S. aureus induced rapid cell death in a dose- and time-dependent manner displaying the characteristic features of apoptosis. Studying the underlying mechanisms we found that the S. aureus-induced apoptosis was associated with a more prominent reduction in expression of the anti-apoptotic protein nuclear transcription factor-kappaB (NF-kappaB). Because expressions of anti-apoptotic Bcl-2, survivin, inhibition of apoptosis protein (cIAP), and X-chromosome-linked inhibitor of apoptosis protein (XIAP) are regulated by NF-kappaB, S. aureus decreased the levels of these proteins in U937 cells through inhibition of NF-kappaB. Moreover, S. aureus induced apoptotic genes (Bax and caspase-3) expression, and exposure of primary monocytes and U937 cells to S. aureus led to caspase-3 activity. Collectively, these data define a pathway that infection of primary monocytes and U937 cells with S. aureus induces a caspase-dependent inhibition of NF-kappaB. CI - Crown Copyright 2010. Published by Elsevier India Pvt Ltd. All rights reserved. FAU - Wang, Jia He AU - Wang JH AD - Department of Geriatrics, Shengjing Hospital of China Medical University, Shenyang, PR China. wangjh1@sj-hospital.org FAU - Zhou, Yi Jun AU - Zhou YJ FAU - He, Ping AU - He P LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20100625 PL - England TA - Microb Pathog JT - Microbial pathogenesis JID - 8606191 RN - 0 (BAX protein, human) RN - 0 (Inhibitor of Apoptosis Proteins) RN - 0 (NF-kappa B) RN - 0 (Proto-Oncogene Proteins c-bcl-2) RN - 0 (X-Linked Inhibitor of Apoptosis Protein) RN - 0 (XIAP protein, human) RN - 0 (bcl-2-Associated X Protein) RN - EC 3.4.22.- (Caspase 3) SB - IM MH - *Apoptosis MH - Caspase 3/biosynthesis MH - Cells, Cultured MH - Down-Regulation MH - *Host-Pathogen Interactions MH - Humans MH - Inhibitor of Apoptosis Proteins/biosynthesis MH - Monocytes/*microbiology MH - NF-kappa B/*biosynthesis MH - Proto-Oncogene Proteins c-bcl-2/biosynthesis MH - *Signal Transduction MH - Staphylococcus aureus/*pathogenicity MH - U937 Cells MH - Up-Regulation MH - X-Linked Inhibitor of Apoptosis Protein/biosynthesis MH - bcl-2-Associated X Protein/biosynthesis EDAT- 2010/07/06 06:00 MHDA- 2010/11/13 06:00 CRDT- 2010/07/06 06:00 PHST- 2010/03/20 00:00 [received] PHST- 2010/06/07 00:00 [revised] PHST- 2010/06/16 00:00 [accepted] PHST- 2010/07/06 06:00 [entrez] PHST- 2010/07/06 06:00 [pubmed] PHST- 2010/11/13 06:00 [medline] AID - S0882-4010(10)00109-9 [pii] AID - 10.1016/j.micpath.2010.06.007 [doi] PST - ppublish SO - Microb Pathog. 2010 Nov;49(5):252-9. doi: 10.1016/j.micpath.2010.06.007. Epub 2010 Jun 25.