PMID- 38508727 OWN - NLM STAT- MEDLINE DCOM- 20240710 LR - 20240806 IS - 1881-7122 (Electronic) IS - 1341-1357 (Print) IS - 0007-5124 (Linking) VI - 73 IP - 3 DP - 2024 Jul 9 TI - Transient receptor potential vanilloid 1 interacts with Toll-like receptor 4 (TLR4)/cluster of differentiation 14 (CD14) signaling pathway in lipopolysaccharide-mediated inflammation in macrophages. PG - 336-346 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, IL-1beta, inducible nitric oxide synthase, and nitric oxide, which were attenuated in Trpv1(-/-) BMDMs. Additionally, the phosphorylation of inhibitor of nuclear factor kappa-Balpha and mitogen-activated protein kinases, as well as the translocation of nuclear factor kappa-B and activator protein 1, were all decreased in LPS-treated Trpv1(-/-) BMDMs. Immunoprecipitation assay revealed that LPS treatment increased the formation of TRPV1-Toll-like receptor 4 (TLR4)-cluster of differentiation 14 (CD14) complex in WT BMDMs. Genetic deletion of TRPV1 in BMDMs impaired the LPS-triggered immune-complex formation of TLR4, myeloid differentiation protein 88, and interleukin-1 receptor-associated kinase, 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, 145, Xingda Road, South District, Taichung 402202, Taiwan. FAU - Tseng, Hsu-Wen AU - Tseng HW AD - Department of Physiology, School of Medicine, National Yang-Ming University, 155, Sec. 2, Linong Street, Taipei 112304, Taiwan. FAU - Chen, Chia-Hui AU - Chen CH AD - Graduate Institute and Department of Physiology, College of Medicine, National Taiwan University, 1, Sec. 1, Jen-Ai Road, Taipei 100233, Taiwan. FAU - Lee, Tzong-Shyuan AU - Lee TS AD - Graduate Institute and Department of Physiology, College of Medicine, National Taiwan University, 1, Sec. 1, Jen-Ai Road, Taipei 100233, Taiwan. LA - eng PT - Journal Article DEP - 20240322 PL - Japan TA - Exp Anim JT - Experimental animals JID - 9604830 RN - 0 (TRPV Cation Channels) RN - 0 (Toll-Like Receptor 4) RN - 0 (Lipopolysaccharides) RN - 0 (TRPV1 protein, mouse) RN - 0 (Tlr4 protein, mouse) RN - 0 (Lipopolysaccharide Receptors) RN - 0 (Cd14 protein, mouse) SB - IM MH - Animals MH - *TRPV Cation Channels/metabolism/genetics/physiology MH - *Toll-Like Receptor 4/metabolism/genetics/physiology MH - *Lipopolysaccharides MH - *Signal Transduction MH - *Macrophages/metabolism MH - *Lipopolysaccharide Receptors/metabolism/genetics MH - *Inflammation/metabolism/genetics MH - Mice MH - Mice, Inbred C57BL MH - Mice, Knockout MH - Male PMC - PMC11254490 OTO - NOTNLM OT - Toll-like receptor 4 (TLR4) OT - inflammation OT - lipopolysaccharide (LPS) OT - macrophage OT - transient receptor potential vanilloid 1 (TRPV1) COIS- The authors declare no conflict of interest. EDAT- 2024/03/21 00:43 MHDA- 2024/07/11 00:42 PMCR- 2024/01/01 CRDT- 2024/03/20 21:43 PHST- 2024/07/11 00:42 [medline] PHST- 2024/03/21 00:43 [pubmed] PHST- 2024/03/20 21:43 [entrez] PHST- 2024/01/01 00:00 [pmc-release] AID - 23-0148 [pii] AID - 10.1538/expanim.23-0148 [doi] PST - ppublish SO - Exp Anim. 2024 Jul 9;73(3):336-346. doi: 10.1538/expanim.23-0148. Epub 2024 Mar 22.