PMID- 31010320
OWN - NLM
STAT- MEDLINE
DCOM- 20190801
LR  - 20190801
IS  - 2169-141X (Electronic)
IS  - 2169-1401 (Linking)
VI  - 47
IP  - 1
DP  - 2019 Dec
TI  - Antagonism of NK-1R using aprepitant suppresses inflammatory response in 
      rheumatoid arthritis fibroblast-like synoviocytes.
PG  - 1628-1634
LID - 10.1080/21691401.2019.1573177 [doi]
AB  - Chronic inflammation in fibroblast-like synoviocytes (FLSs) induced by 
      pro-inflammatory cytokines such as TNF-alpha plays a key role in the pathogenesis of 
      rheumatoid arthritis (RA). The neurokinin-1 receptor (NK-1R) is one of the G 
      protein-coupled receptors (GPCRs) mediating the intracellular signalling of 
      substance P (SP). However, the possible implications of NK-1R in rheumatoid 
      arthritis fibroblast-like synoviocytes (RA-FLSs) and the pathogenesis of RA have 
      not yet been reported. In the current study, we report that NK-1R is expressed in 
      FLSs. Importantly, NK-1R expression was found to be significantly increased in 
      RA-FLSs compared to normal FLSs. Interestingly, we found that treatment with 
      tumour necrosis factor (TNF)-alpha increased the expression of NK-1R at both the gene 
      and protein levels. Treatment with the NK-1R antagonist aprepitant reduced 
      TNF-alpha-induced expression of NADPH oxidase 4 (NOX-4) and generation of reactive 
      oxygen species (ROS) in FLSs. Our results also display that blockage of NF-1R 
      using aprepitant inhibited TNF-alpha-induced expression and secretion of 
      proinflammatory cytokines, including interleukin-1beta (IL-1beta), IL-6, and IL-8. 
      Consistently, aprepitant prevented TNF-alpha-induced expression of matrix 
      metalloproteinases (MMPs), including matrix metalloproteinase-3 (MMP-3) and 
      matrix metalloproteinase-13 (MMP-13). Mechanistically, our data demonstrate that 
      treatment with aprepitant inhibited TNF-alpha-induced phosphorylation and degradation 
      of inhibitor of NF-kappaB (IkappaBalpha). Notably, aprepitant attenuated TNF-alpha-induced 
      nuclear translocation of nuclear factor kappaB (NF-kappaB) p65 and reduced luciferase 
      activity of NF-kappaB in FLSs. The findings implicated a novel function of NK-1R in 
      RA-FLSs. Blockage of NK-1R using its specific antagonist aprepitant might provide 
      a new therapeutic strategy for RA.
FAU - Liu, Xiaoping
AU  - Liu X
AD  - a Department of Rheumatology , Dongfang Hospital of Beijing University of Chinese 
      Medicine , Beijing , China.
FAU - Zhu, Yuelan
AU  - Zhu Y
AD  - a Department of Rheumatology , Dongfang Hospital of Beijing University of Chinese 
      Medicine , Beijing , China.
FAU - Zheng, Wei
AU  - Zheng W
AD  - b Internal medicine of TCM , Beijing University of Chinese Medicine , Beijing , 
      China.
FAU - Qian, Tangliang
AU  - Qian T
AD  - b Internal medicine of TCM , Beijing University of Chinese Medicine , Beijing , 
      China.
FAU - Wang, Haiyu
AU  - Wang H
AD  - b Internal medicine of TCM , Beijing University of Chinese Medicine , Beijing , 
      China.
FAU - Hou, Xiujuan
AU  - Hou X
AD  - a Department of Rheumatology , Dongfang Hospital of Beijing University of Chinese 
      Medicine , Beijing , China.
LA  - eng
PT  - Journal Article
PL  - England
TA  - Artif Cells Nanomed Biotechnol
JT  - Artificial cells, nanomedicine, and biotechnology
JID - 101594777
RN  - 0 (NF-kappa B)
RN  - 0 (Neurokinin-1 Receptor Antagonists)
RN  - 0 (Receptors, Neurokinin-1)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 139874-52-5 (NF-KappaB Inhibitor alpha)
RN  - 1NF15YR6UY (Aprepitant)
RN  - EC 3.4.24.- (Matrix Metalloproteinase 13)
RN  - EC 3.4.24.17 (Matrix Metalloproteinase 3)
MH  - Aprepitant/*pharmacology/therapeutic use
MH  - Arthritis, Rheumatoid/drug therapy/genetics/*metabolism/*pathology
MH  - Fibroblasts/*pathology
MH  - Gene Expression Regulation/drug effects
MH  - Humans
MH  - Inflammation/drug therapy
MH  - Matrix Metalloproteinase 13/metabolism
MH  - Matrix Metalloproteinase 3/metabolism
MH  - NF-KappaB Inhibitor alpha/metabolism
MH  - NF-kappa B/metabolism
MH  - Neurokinin-1 Receptor Antagonists/*pharmacology/therapeutic use
MH  - Oxidative Stress/drug effects
MH  - Receptors, Neurokinin-1/genetics/*metabolism
MH  - Signal Transduction/drug effects
MH  - Synoviocytes/*drug effects/metabolism/pathology
MH  - Tumor Necrosis Factor-alpha/metabolism
OTO - NOTNLM
OT  - NF-kappaB
OT  - NK-1R
OT  - Rheumatoid arthritis
OT  - TNF-alpha
OT  - aprepitant
OT  - matrix metalloproteinases
EDAT- 2019/04/24 06:00
MHDA- 2019/08/02 06:00
CRDT- 2019/04/24 06:00
PHST- 2019/04/24 06:00 [entrez]
PHST- 2019/04/24 06:00 [pubmed]
PHST- 2019/08/02 06:00 [medline]
AID - 10.1080/21691401.2019.1573177 [doi]
PST - ppublish
SO  - Artif Cells Nanomed Biotechnol. 2019 Dec;47(1):1628-1634. doi: 
      10.1080/21691401.2019.1573177.