PMID- 26632487
OWN - NLM
STAT- MEDLINE
DCOM- 20170210
LR  - 20201209
IS  - 2567-689X (Electronic)
IS  - 0340-6245 (Linking)
VI  - 115
IP  - 3
DP  - 2016 Mar
TI  - Staphylococcal SSL5-induced platelet microparticles provoke proinflammatory 
      responses via the CD40/TRAF6/NFkappaB signalling pathway in monocytes.
PG  - 632-45
LID - 10.1160/TH15-04-0322 [doi]
AB  - Pathogens-induced platelet activation contributes to inflammation in 
      cardiovascular diseases, but underlying mechanisms remain elusive. Staphylococcal 
      superantigen-like protein 5 (SSL5) is a known activator of platelets. Here we 
      examined whether SSL5 is implicated in Staphylococcus aureus (S. aureus)-induced 
      inflammation and potential mechanisms involved. As expected, we show that SSL5 
      activates human platelets and induces generation of platelet microparticles 
      (PMPs). Flow cytometry and scanning electron microscopy studies demonstrate that 
      SSL5-induced PMPs (SSL5-PMPs) bind to monocytes, causing aggregate formation. In 
      addition, SSL5-PMPs provoke monocyte expression and release of inflammatory 
      mediators, including interleukin-1beta (IL-1beta), tumour necrosis factor-alpha (TNFalpha), 
      monocyte chemoattractant protein-1 (MCP-1) and matrix metalloproteinase-9 (MMP-9) 
      in a dose- and time-dependent manner. SSL5-PMPs also enhance MCP-1-induced 
      monocyte migration. Blockade of CD40 and CD40 ligand (CD40L) interactions with 
      neutralising antibodies significantly reduce monocyte release of inflammatory 
      mediators and migration induced by SSL5-PMPs. SiRNA-mediated silencing of CD40 or 
      TNF receptor (TNFR)-associated factor 6 (TRAF6) gene largely abrogates 
      phosphorylation and nuclear translocation of NFkappaB (p65). In conclusion, SSL5 
      provokes the release of inflammatory mediators in monocytes, at least in part, 
      via PMPs-mediated activation of the CD40/TRAF6/NFkappaB signalling pathway, though it 
      normally inhibits leukocyte function. Our findings thus reveal a novel mechanism 
      by which S. aureus induces inflammation.
FAU - Bei, Jun-Jie
AU  - Bei JJ
FAU - Liu, Chuan
AU  - Liu C
FAU - Peng, Song
AU  - Peng S
FAU - Liu, Cheng-Hai
AU  - Liu CH
FAU - Zhao, Wei-Bo
AU  - Zhao WB
FAU - Qu, Xiao-Long
AU  - Qu XL
FAU - Chen, Qiang
AU  - Chen Q
FAU - Zhou, Zhou
AU  - Zhou Z
FAU - Yu, Zheng-Ping
AU  - Yu ZP
FAU - Peter, Karlheinz
AU  - Peter K
FAU - Hu, Hou-Yuan
AU  - Hu HY
AD  - Hou-Yuan Hu, Department of Cardiology, Southwest Hospital, Third Military Medical 
      University, 29 Gaotanyan Street, Shapingba District, Chongqing 400038, China, 
      Tel.: +86 23 68765167, Fax: +86 23 65317511, E-mail: houyuanhu@hotmail.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20151203
PL  - Germany
TA  - Thromb Haemost
JT  - Thrombosis and haemostasis
JID - 7608063
RN  - 0 (Bacterial Proteins)
RN  - 0 (CCL2 protein, human)
RN  - 0 (CD40 Antigens)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Interleukin-1beta)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (NF-kappa B p50 Subunit)
RN  - 0 (NFKB1 protein, human)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (Receptors, Tumor Necrosis Factor)
RN  - 0 (Recombinant Proteins)
RN  - 0 (SSL5 protein, Staphylococcus aureus)
RN  - 0 (TNF Receptor-Associated Factor 6)
RN  - 0 (Tifab protein, human)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - EC 3.4.24.35 (MMP9 protein, human)
RN  - EC 3.4.24.35 (Matrix Metalloproteinase 9)
SB  - IM
MH  - Active Transport, Cell Nucleus
MH  - Bacterial Proteins/*metabolism
MH  - Blood Platelets/metabolism
MH  - CD40 Antigens/*metabolism
MH  - Cell Movement
MH  - Cell-Derived Microparticles
MH  - Chemokine CCL2/metabolism
MH  - Flow Cytometry
MH  - Gene Silencing
MH  - Humans
MH  - Inflammation
MH  - Interleukin-1beta/metabolism
MH  - Intracellular Signaling Peptides and Proteins
MH  - Matrix Metalloproteinase 9/metabolism
MH  - Monocytes/*cytology
MH  - NF-kappa B p50 Subunit/*metabolism
MH  - RNA Interference
MH  - RNA, Small Interfering/metabolism
MH  - Receptors, Tumor Necrosis Factor/metabolism
MH  - Recombinant Proteins/metabolism
MH  - Signal Transduction
MH  - Staphylococcus aureus
MH  - TNF Receptor-Associated Factor 6/*metabolism
MH  - Tumor Necrosis Factor-alpha/metabolism
OTO - NOTNLM
OT  - CD40 ligand
OT  - Staphylococcal superantigen-like protein 5
OT  - inflammation
OT  - monocytes
OT  - platelet microparticles
EDAT- 2015/12/04 06:00
MHDA- 2017/02/12 06:00
CRDT- 2015/12/04 06:00
PHST- 2015/04/19 00:00 [received]
PHST- 2015/10/28 00:00 [accepted]
PHST- 2015/12/04 06:00 [entrez]
PHST- 2015/12/04 06:00 [pubmed]
PHST- 2017/02/12 06:00 [medline]
AID - 15-04-0322 [pii]
AID - 10.1160/TH15-04-0322 [doi]
PST - ppublish
SO  - Thromb Haemost. 2016 Mar;115(3):632-45. doi: 10.1160/TH15-04-0322. Epub 2015 Dec 
      3.