PMID- 30761006
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20200930
IS  - 1663-9812 (Print)
IS  - 1663-9812 (Electronic)
IS  - 1663-9812 (Linking)
VI  - 10
DP  - 2019
TI  - CRP-Induced NLRP3 Inflammasome Activation Increases LDL Transcytosis Across 
      Endothelial Cells.
PG  - 40
LID - 10.3389/fphar.2019.00040 [doi]
LID - 40
AB  - The NLRP3 inflammasome, a multiprotein cytosolic complex that activates the IL-1 
      family of cytokines, plays an important role in atherosclerosis (AS). 
      High-sensitivity c-reactive protein (hs-CRP) is widely recognized as a major 
      cardiovascular risk predictor and recent studies name NLRP3 as a predictor of CRP 
      levels. Mounting evidence has indicated that subendothelial retention of 
      apolipoprotein B100-containing lipoproteins, such as low-density lipoprotein 
      (LDL), is the initial step of atherogenesis, and is usually termed the "response 
      to retention hypothesis." We previously reported that CRP promotes AS by directly 
      increasing LDL transcytosis across endothelial cells (ECs). The present study 
      aims to investigate the effects of CRP on NLRP3 inflammasome activation and the 
      role of the NLRP3 inflammasome in CRP-induced LDL transcytosis. We found that CRP 
      upregulated NF-kappaB activity, the NF-kappaB inhibitor (BAY-11-7082) and Fcgamma receptors 
      (FcgammaRs) inhibitor (CD32/64Ab) blocked CRP-induced NF-kappaB activation. CRP also 
      induced expression of pro-IL-1beta and NLRP3, while BAY and CD32/64 Ab suppressed 
      CRP-mediated expression of NLRP3 and pro-IL-1beta. Moreover, CRP activated the NLRP3 
      inflammasome in ECs. NADPH oxidase inhibitor, diphenylene iodonium (DPI) and 
      dithiothreitol (DTT), a broad-spectrum P2 receptor inhibitor, oxidized ATP 
      (oATP), and a broad inhibitor of cysteine proteases, E-64d, inhibited CRP-induced 
      NLRP3 inflammasome activation. Furthermore, NLRP3 siRNA and caspase-1 inhibitor 
      blocked CRP-mediated LDL transcytosis across ECs. In conclusion, NLRP3 
      inflammasome activation was shown to be involved in CRP-mediated LDL transcytosis 
      across ECs. CRP not only increased the expression of pro-IL-1beta and NLRP3 via the 
      FcgammaRs/NF-kappaB pathway, but also promoted NLRP3 inflammasome activation and IL-1beta 
      maturation by upregulation of reactive oxygen species (ROS) levels, purinergic 
      receptor signaling, and activation of cysteine proteases.
FAU - Bian, Fang
AU  - Bian F
AD  - Department of Endocrinology, Institute of Geriatric Medicine, Liyuan Hospital, 
      Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 
      China.
AD  - Department of Pharmacy, Xiangyang Central Hospital, Affiliated Hospital of Hubei 
      University of Arts and Science, Xiangyang, China.
FAU - Yang, Xiao-Yan
AU  - Yang XY
AD  - Department of Pharmacology, Hubei Key Laboratory of Drug Target Research and 
      Pharmacodynamic Evaluation, School of Basic Medicine, Tongji Medical College, 
      Huazhong University of Science and Technology, Wuhan, China.
FAU - Xu, Gao
AU  - Xu G
AD  - Department of Pharmacy, Wuhan Union Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, Wuhan, China.
FAU - Zheng, Tao
AU  - Zheng T
AD  - Department of Endocrinology, Institute of Geriatric Medicine, Liyuan Hospital, 
      Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 
      China.
AD  - Department of Pharmacy, Taihe Hospital, Hubei University of Medicine, Shiyan, 
      China.
FAU - Jin, Si
AU  - Jin S
AD  - Department of Endocrinology, Institute of Geriatric Medicine, Liyuan Hospital, 
      Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 
      China.
LA  - eng
PT  - Journal Article
DEP - 20190130
PL  - Switzerland
TA  - Front Pharmacol
JT  - Frontiers in pharmacology
JID - 101548923
PMC - PMC6363700
OTO - NOTNLM
OT  - C-reactive protein
OT  - NLRP3 inflammasome
OT  - endothelial cells
OT  - low density lipoprotein
OT  - transcytosis
EDAT- 2019/02/15 06:00
MHDA- 2019/02/15 06:01
PMCR- 2019/01/30
CRDT- 2019/02/15 06:00
PHST- 2018/09/25 00:00 [received]
PHST- 2019/01/14 00:00 [accepted]
PHST- 2019/02/15 06:00 [entrez]
PHST- 2019/02/15 06:00 [pubmed]
PHST- 2019/02/15 06:01 [medline]
PHST- 2019/01/30 00:00 [pmc-release]
AID - 10.3389/fphar.2019.00040 [doi]
PST - epublish
SO  - Front Pharmacol. 2019 Jan 30;10:40. doi: 10.3389/fphar.2019.00040. eCollection 
      2019.