PMID- 28855621
OWN - NLM
STAT- MEDLINE
DCOM- 20190422
LR  - 20190422
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 7
IP  - 1
DP  - 2017 Aug 30
TI  - Immune activated monocyte exosomes alter microRNAs in brain endothelial cells and 
      initiate an inflammatory response through the TLR4/MyD88 pathway.
PG  - 9954
LID - 10.1038/s41598-017-10449-0 [doi]
LID - 9954
AB  - The host immune response is critical for homeostasis; however, when chronic low 
      level activation of the immune response with or without the driver continues, a 
      cascade of events can trigger immunological dysfunction. Monocytes are key 
      peripheral sensors of the immune response and their activation is instrumental in 
      the development of cognitive impairment. Here, we show that monocytes activated 
      by interferon alpha, lipopolysaccharide or a combination of both generate 
      exosomes carrying significantly altered microRNA profiles compared to 
      non-activated monocytes. These exosomes alone can activate human brain 
      microvascular endothelial cells to stimulate adhesion molecules, CCL2, ICAM1, 
      VCAM1 and cytokines, IL1beta and IL6. This activation is through the toll like 
      receptor 4 (TLR4)/myeloid differentiation primary response gene 88 (MyD88) 
      pathway that activates nuclear factor-kappaB and increases monocyte chemotaxis. 
      Inhibition of monocyte exosome release reverses endothelial cell activation and 
      monocyte chemotaxis. Our study suggests that activated monocytes have an impact 
      on brain vascular function through intercellular exosome signaling.
FAU - Dalvi, Pranjali
AU  - Dalvi P
AD  - Department of Laboratory Medicine, Veterans Administration Medical Center, San 
      Francisco, CA, USA.
FAU - Sun, Bing
AU  - Sun B
AD  - Department of Laboratory Medicine, Veterans Administration Medical Center, San 
      Francisco, CA, USA.
FAU - Tang, Norina
AU  - Tang N
AD  - Department of Laboratory Medicine, Veterans Administration Medical Center, San 
      Francisco, CA, USA.
FAU - Pulliam, Lynn
AU  - Pulliam L
AD  - Department of Laboratory Medicine, Veterans Administration Medical Center, San 
      Francisco, CA, USA. Lynn.Pulliam@ucsf.edu.
AD  - Departments of Laboratory Medicine and Medicine, University of California, San 
      Francisco, CA, USA. Lynn.Pulliam@ucsf.edu.
LA  - eng
PT  - Journal Article
DEP - 20170830
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 0 (Cytokines)
RN  - 0 (MYD88 protein, human)
RN  - 0 (MicroRNAs)
RN  - 0 (Myeloid Differentiation Factor 88)
RN  - 0 (TLR4 protein, human)
RN  - 0 (Toll-Like Receptor 4)
SB  - IM
MH  - Blotting, Western
MH  - Cells, Cultured
MH  - Coculture Techniques
MH  - Cytokines/*metabolism
MH  - Endothelial Cells/*immunology/metabolism
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Exosomes/*metabolism
MH  - Gene Expression Profiling
MH  - Humans
MH  - MicroRNAs/*analysis
MH  - Monocytes/*immunology/metabolism
MH  - Myeloid Differentiation Factor 88/*metabolism
MH  - Real-Time Polymerase Chain Reaction
MH  - Toll-Like Receptor 4/*metabolism
PMC - PMC5577170
COIS- The authors declare that they have no competing interests.
EDAT- 2017/09/01 06:00
MHDA- 2019/04/23 06:00
PMCR- 2017/08/30
CRDT- 2017/09/01 06:00
PHST- 2017/05/24 00:00 [received]
PHST- 2017/08/08 00:00 [accepted]
PHST- 2017/09/01 06:00 [entrez]
PHST- 2017/09/01 06:00 [pubmed]
PHST- 2019/04/23 06:00 [medline]
PHST- 2017/08/30 00:00 [pmc-release]
AID - 10.1038/s41598-017-10449-0 [pii]
AID - 10449 [pii]
AID - 10.1038/s41598-017-10449-0 [doi]
PST - epublish
SO  - Sci Rep. 2017 Aug 30;7(1):9954. doi: 10.1038/s41598-017-10449-0.