PMID- 38508727
OWN - NLM
STAT- Publisher
LR  - 20240320
IS  - 1881-7122 (Electronic)
IS  - 0007-5124 (Linking)
DP  - 2024 Mar 21
TI  - Transient receptor potential vanilloid 1 interacts with TLR4/CD14 signaling 
      pathway in lipopolysaccharide-mediated inflammation in macrophages.
LID - 10.1538/expanim.23-0148 [doi]
AB  - Transient receptor potential vanilloid 1 (TRPV1), a ligand-gated cation channel, 
      is a receptor for vanilloids on sensory neurons and is also activated by 
      capsaicin, heat, protons, arachidonic acid metabolites, and inflammatory 
      mediators on neuronal or non-neuronal cells. However, the role of the TRPV1 
      receptor in pro-inflammatory cytokine secretion and its potential regulatory 
      mechanisms in lipopolysaccharide (LPS)-induced inflammation has yet to be 
      entirely understood. To investigate the role and regulatory mechanism of the 
      TRPV1 receptor in regulating LPS-induced inflammatory responses, bone 
      marrow-derived macrophages (BMDMs) harvested from wild-type (WT) and TRPV1 
      deficient (Trpv1(-/-)) mice were used as the cell model. In WT BMDMs, LPS induced 
      an increase in the levels of tumor necrosis factor-alpha, interleukin-1beta, inducible 
      nitric oxide synthase (iNOS), and nitric oxide, which were attenuated in 
      Trpv1(-/-) BMDMs. Additionally, the phosphorylation of IkappaBalpha and mitogen-activated 
      protein kinases, as well as the translocation of NF-kappaB and AP-1, were all 
      decreased in LPS-treated Trpv1(-/-) BMDMs. Immunoprecipitation assay revealed 
      that LPS treatment increased the formation of TRPV1-TLR4-CD14 complex in WT 
      BMDMs. Genetic deletion of TRPV1 in BMDMs impaired the LPS-triggered 
      immune-complex formation of TLR4, MyD88, and IRAK, all of which are essential 
      regulators in LPS-induced activation of the TLR4 signaling pathway. Moreover, 
      genetic deletion of TRPV1 prevented the LPS-induced lethality and 
      pro-inflammatory production in mice. In conclusion, the TRPV1 receptor may 
      positively regulate the LPS-mediated inflammatory responses in macrophages by 
      increasing the interaction with the TLR4-CD14 complex and activating the 
      downstream signaling cascade.
FAU - Hsu, Julia Chu-Ning
AU  - Hsu JC
AD  - Department of Veterinary Medicine, College of Veterinary Medicine, National Chung 
      Hsing University.
FAU - Tseng, Hsu-Wen
AU  - Tseng HW
AD  - Department of Physiology, School of Medicine, National Yang-Ming University.
FAU - Chen, Chia-Hui
AU  - Chen CH
AD  - Graduate Institute and Department of Physiology, College of Medicine, National 
      Taiwan University.
FAU - Lee, Tzong-Shyuan
AU  - Lee TS
AD  - Graduate Institute and Department of Physiology, College of Medicine, National 
      Taiwan University.
LA  - eng
PT  - Journal Article
DEP - 20240321
PL  - Japan
TA  - Exp Anim
JT  - Experimental animals
JID - 9604830
SB  - IM
OTO - NOTNLM
OT  - inflammation
OT  - lipopolysaccharide (LPS)
OT  - macrophage
OT  - toll-like receptor 4 (TLR4)
OT  - transient receptor potential vanilloid 1 (TRPV1)
EDAT- 2024/03/21 00:43
MHDA- 2024/03/21 00:43
CRDT- 2024/03/20 21:43
PHST- 2024/03/21 00:43 [medline]
PHST- 2024/03/21 00:43 [pubmed]
PHST- 2024/03/20 21:43 [entrez]
AID - 10.1538/expanim.23-0148 [doi]
PST - aheadofprint
SO  - Exp Anim. 2024 Mar 21. doi: 10.1538/expanim.23-0148.