PMID- 28607410
OWN - NLM
STAT- MEDLINE
DCOM- 20190107
LR  - 20190107
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 7
IP  - 1
DP  - 2017 Jun 12
TI  - DC-SIGN and Toll-like receptor 4 mediate oxidized low-density lipoprotein-induced 
      inflammatory responses in macrophages.
PG  - 3296
LID - 10.1038/s41598-017-03740-7 [doi]
LID - 3296
AB  - The regulation of inflammatory responses by innate immune receptors is recognized 
      as a crucial step in the development of atherosclerosis, although the precise 
      molecular mechanisms remain to be elucidated. This study focused on illustrating 
      the roles of dendritic cell-specific intercellular adhesion molecule-3-grabbing 
      non-integrin (DC-SIGN)- and Toll-like receptor 4 (TLR4)-regulated inflammatory 
      responses in macrophages. We found that DC-SIGN expression levels were increased 
      in macrophages of atherosclerotic plaques. Oxidized low-density lipoprotein 
      (oxLDL) significantly enhanced DC-SIGN protein expression levels after a 
      short-term exposure. Knockdown of DC-SIGN decreased expression and secretion of 
      interleukin 1-beta (IL1-beta), monocyte chemo-attractant protein 1 (MCP-1), tumor 
      necrosis factor-alpha (TNFalpha) and matrix metalloproteinase-9 (MMP-9). 
      Immunofluorescence studies demonstrated that DC-SIGN and TLR4 co-localized in 
      regions of the plaques. Moreover, DC-SIGN was co-expressed with TLR4 on the 
      plasma membrane after oxLDL stimulation. The presence of an endogenous 
      interaction and the results of the in vitro pull-down assays revealed that 
      DC-SIGN binds directly with TLR4. We also present evidence that DC-SIGN mediates 
      TLR4-regulated NFkappaB activation but not activation of p38 and JNK. Our results 
      suggest an essential role of DC-SIGN/TLR4 signaling in macrophages in the 
      pathogenesis of atherosclerosis.
FAU - Yang, Ke
AU  - Yang K
AD  - Institute of Cardiovascular Disease, Ruijin hospital, Jiaotong University School 
      of Medicine, Shanghai, 200025, China.
FAU - Liu, Xinhe
AU  - Liu X
AD  - Department of Pediatrics, Ruijin Hospital, Shanghai Jiaotong University School of 
      Medicine, Shanghai, 200025, China.
FAU - Liu, Yan
AU  - Liu Y
AD  - Institute of Cardiovascular Disease, Ruijin hospital, Jiaotong University School 
      of Medicine, Shanghai, 200025, China.
AD  - Department of Cardiology, Shanghai Ninth People's Hospital, Shanghai Jiaotong 
      University School of Medicine, Shanghai, 200025, China.
FAU - Wang, Xinqiong
AU  - Wang X
AD  - Department of Pediatrics, Ruijin Hospital, Shanghai Jiaotong University School of 
      Medicine, Shanghai, 200025, China.
FAU - Cao, Lijuan
AU  - Cao L
AD  - Institute of Cardiovascular Disease, Ruijin hospital, Jiaotong University School 
      of Medicine, Shanghai, 200025, China.
FAU - Zhang, Xiaojie
AU  - Zhang X
AD  - Institute of Cardiovascular Disease, Ruijin hospital, Jiaotong University School 
      of Medicine, Shanghai, 200025, China.
FAU - Xu, Chundi
AU  - Xu C
AD  - Department of Pediatrics, Ruijin Hospital, Shanghai Jiaotong University School of 
      Medicine, Shanghai, 200025, China.
FAU - Shen, Weifeng
AU  - Shen W
AD  - Institute of Cardiovascular Disease, Ruijin hospital, Jiaotong University School 
      of Medicine, Shanghai, 200025, China. rjshenweifeng@gmail.com.
FAU - Zhou, Tong
AU  - Zhou T
AD  - Department of Pediatrics, Ruijin Hospital, Shanghai Jiaotong University School of 
      Medicine, Shanghai, 200025, China. zhoutong_cn@hotmail.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20170612
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 0 (Cell Adhesion Molecules)
RN  - 0 (Cytokines)
RN  - 0 (DC-specific ICAM-3 grabbing nonintegrin)
RN  - 0 (Inflammation Mediators)
RN  - 0 (Lectins, C-Type)
RN  - 0 (Lipoproteins, LDL)
RN  - 0 (Receptors, Cell Surface)
RN  - 0 (Toll-Like Receptor 4)
RN  - 0 (Transcription Factor RelA)
RN  - 0 (oxidized low density lipoprotein)
SB  - IM
MH  - Atherosclerosis/metabolism/pathology
MH  - Cell Adhesion Molecules/*metabolism
MH  - Cytokines/metabolism
MH  - Female
MH  - Gene Knockdown Techniques
MH  - HEK293 Cells
MH  - Humans
MH  - Inflammation/*pathology
MH  - Inflammation Mediators/metabolism
MH  - Lectins, C-Type/*metabolism
MH  - Lipoproteins, LDL/*metabolism
MH  - Macrophages/*metabolism/*pathology
MH  - Male
MH  - Middle Aged
MH  - Plaque, Atherosclerotic/pathology
MH  - Protein Binding
MH  - Receptors, Cell Surface/*metabolism
MH  - Toll-Like Receptor 4/*metabolism
MH  - Transcription Factor RelA/metabolism
PMC - PMC5468253
COIS- The authors declare that they have no competing interests.
EDAT- 2017/06/14 06:00
MHDA- 2019/01/08 06:00
PMCR- 2017/06/12
CRDT- 2017/06/14 06:00
PHST- 2016/04/27 00:00 [received]
PHST- 2017/05/05 00:00 [accepted]
PHST- 2017/06/14 06:00 [entrez]
PHST- 2017/06/14 06:00 [pubmed]
PHST- 2019/01/08 06:00 [medline]
PHST- 2017/06/12 00:00 [pmc-release]
AID - 10.1038/s41598-017-03740-7 [pii]
AID - 3740 [pii]
AID - 10.1038/s41598-017-03740-7 [doi]
PST - epublish
SO  - Sci Rep. 2017 Jun 12;7(1):3296. doi: 10.1038/s41598-017-03740-7.