PMID- 22745684
OWN - NLM
STAT- MEDLINE
DCOM- 20121130
LR  - 20211021
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 7
IP  - 6
DP  - 2012
TI  - Damage associated molecular pattern molecule-induced microRNAs (DAMPmiRs) in 
      human peripheral blood mononuclear cells.
PG  - e38899
LID - 10.1371/journal.pone.0038899 [doi]
LID - e38899
AB  - Endogenous damage associated molecular pattern molecules (DAMPs) released from 
      necrotic, damaged or stressed cells are associated with an inflammatory response. 
      Whether the microRNA (miR) expression signature of this response is different 
      from that of a pathogen associated molecular pattern (PAMP)-stimulated 
      inflammatory response is unknown. We report here that miR-34c and miR-214 are 
      significantly expressed in fresh human peripheral blood mononuclear cells (PBMCs) 
      exposed to DAMP-containing freeze-thaw lysates, or to conditioned media from 
      serum-starved and glucose-deprived cells (p<6x10(-4) and p<3.7x10(-3)), 
      respectively. Interestingly, only miR-34c expression was differentially expressed 
      in PBMCs exposed to freeze-thaw lysates or conditioned media from wildtype High 
      Mobility Group B1 (HMGB1(+/+)) mouse embryonic fibroblast (MEF) cells, when 
      compared to cultures exposed to lysates or conditioned media from HMGB1(-/-) 
      MEFs. miR-155 expression in these cultures was negligible, but was significantly 
      expressed in PBMCs stimulated with Lipopolysaccahride (LPS) or most other 
      Toll-like receptor (TLR) ligands, making it the prototypic "PAMPmiR". Exposure to 
      a damaged human colorectal carcinoma cell line lysate (HCT116) similarly resulted 
      in increased miR-34c and miR-214 levels. When PBMCs were pre-transfected with 
      anti-miR-34c and then exposed to lysate, expression levels of IKKgamma mRNA, a 
      putative target of miR-34c, increased, while protein levels of IKKgamma in cultures 
      transfected with a pre-miR-34c were abrogated. Levels of miR-34c expression (as 
      well as pro-inflammatory cytokines, IL-1beta and TNFalpha) decreased when PBMC cultures 
      were briefly pre-incubated with the K(+) channel (inflammasome) inhibitor, 
      glybenclamide, suggesting that inflammasome activation is upstream of miR-34c 
      expression in response to DAMPs. Our findings demonstrate that a specific 
      microRNA expression signature is associated with the inflammatory response to 
      damaged/injured cells and carries implications for many acute and chronic 
      inflammatory disorders.
FAU - Unlu, Sebnem
AU  - Unlu S
AD  - Department of Surgery, School of Medicine, University of Pittsburgh, Pittsburgh, 
      Pennsylvania, United States of America. unlus@upmc.edu
FAU - Tang, Siuwah
AU  - Tang S
FAU - Wang, Ena
AU  - Wang E
FAU - Martinez, Ivan
AU  - Martinez I
FAU - Tang, Daolin
AU  - Tang D
FAU - Bianchi, Marco E
AU  - Bianchi ME
FAU - Zeh, Herbert J 3rd
AU  - Zeh HJ 3rd
FAU - Lotze, Michael T
AU  - Lotze MT
LA  - eng
GR  - P01 CA101944/CA/NCI NIH HHS/United States
GR  - UL1 TR000005/TR/NCATS NIH HHS/United States
GR  - P01 CA 101944-04/CA/NCI NIH HHS/United States
GR  - 1U54RR023506-01/RR/NCRR NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20120622
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Culture Media, Conditioned)
RN  - 0 (Inflammasomes)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (MIRN155 microRNA, human)
RN  - 0 (MIRN214 microRNA, human)
RN  - 0 (MicroRNAs)
SB  - IM
EIN - PLoS One. 2012;7(8). doi: 
      10.1371/annotation/18ec64ae-e086-446c-b63c-a71fa2bba046. Wang, E na [corrected to 
      Wang, Ena]
MH  - Animals
MH  - Cell Line
MH  - Cell Line, Tumor
MH  - Culture Media, Conditioned/pharmacology
MH  - Humans
MH  - Inflammasomes/metabolism
MH  - Leukocytes, Mononuclear/*drug effects/*metabolism
MH  - Lipopolysaccharides/pharmacology
MH  - Mice
MH  - MicroRNAs/*metabolism
PMC - PMC3382181
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2012/06/30 06:00
MHDA- 2012/12/10 06:00
PMCR- 2012/06/22
CRDT- 2012/06/30 06:00
PHST- 2012/02/09 00:00 [received]
PHST- 2012/05/14 00:00 [accepted]
PHST- 2012/06/30 06:00 [entrez]
PHST- 2012/06/30 06:00 [pubmed]
PHST- 2012/12/10 06:00 [medline]
PHST- 2012/06/22 00:00 [pmc-release]
AID - PONE-D-12-05468 [pii]
AID - 10.1371/journal.pone.0038899 [doi]
PST - ppublish
SO  - PLoS One. 2012;7(6):e38899. doi: 10.1371/journal.pone.0038899. Epub 2012 Jun 22.