The transient receptor potential vanilloid 1 (TRPV1) is a non-selective cation channel expressed on sensory neurons and immune cells. We hypothesize that TRPV1 plays a role in human eosinophil function and is modulated by inflammatory conditions. TRPV1 expression on human eosinophils was examined by qPCR, flow cytometry, and immunohistochemistry, respectively. TRPV1 functionality was analyzed by investigating calcium flux, apoptosis, modulation by cytokines and acidic pH, and CD69 externalization using flow cytometry. Activation of TRPV1 induced calcium influx and prolonged survival. Although eosinophils were not directly activated by TRPV1 agonists, activation by IL-3 or GM-CSF was mainly restricted to TRPV1-positive eosinophils. TRPV1 surface content was increased by acidic pH, IL-3, IL-31, IL-33, TSLP, TNF-α, BDNF, and NGF-β. Interestingly, TRPV1 was also expressed by eosinophils located in proximity to peripheral nerves in atopic dermatitis (AD) skin. In conclusion, eosinophils express functional TRPV1 channels which are increased by extracellular acidification and AD-related cytokines. Since eosinophils also express TRPV1 in AD skin, our results indicate an important role of TRPV1 for neuroimmune interaction mechanisms in itchy, inflammatory skin diseases, like AD.
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http://dx.doi.org/10.3390/ijms25031922 | DOI Listing |
Truncated TrkB (TrkBT1), traditionally considered a dominant-negative regulator of full-length TrkB (TrkBTK+), remains poorly understood in peripheral sensory neurons, particularly nociceptors. Furthermore, sensory neuronal TrkB expression and function has been traditionally associated with non-nociceptive neurons, particularly Aδ low-threshold mechanoreceptors. This study challenges prevailing assumptions by demonstrating that TrkBT1 is the predominant TrkB isoform expressed in sensory neurons and plays a functional role in modulating neuronal activity.
View Article and Find Full Text PDFThe capsaicin receptor, TRPV1, mediates the detection of harmful chemical and thermal stimuli. Overactivation of TRPV1 can lead to cellular damage or death through excitotoxicity, a phenomenon associated with painful neuropathy and the paradoxical use of capsaicin as an analgesic. We exploited capsaicin-evoked death to conduct a systematic analysis of excitotoxicity through a genome-wide CRISPRi screen, thereby revealing a comprehensive network of regulatory pathways.
View Article and Find Full Text PDFExp Eye Res
January 2025
Laboratory of Ocular Immunology, Transplantation and Regeneration, Schepens Eye Research Institute of Massachusetts Eye and Ear, Department of Ophthalmology, Harvard Medical School, Boston, MA. Electronic address:
Substance P (SP) expressed by corneal nerves, is an 11-amino acid long neuropeptide from the tachykinin family, encoded by the Tac1 gene, and binds to neurokinin receptors. SP overexpression is associated with various pathological responses in the cornea including vasodilation, pain, inflammation, and angiogenesis in the normally avascular tissue. This study investigates the role of neurokinin-1 receptor (NK-1R) mediated signaling in nociception, nerve regeneration, and neuronal activation following mechanical corneal injury in mice.
View Article and Find Full Text PDFCurr Top Med Chem
January 2025
School of Pharmacy & School of Biological and Food Engineering, Changzhou University, Changzhou, 213164, Jiangsu, PR China.
Transient receptor potential vanilloid (TRPV) channels are a member of the TRP superfamily, which consists of six proteins and is expressed in many neuronal and non-neuronal cells. Among them, TRPV1-4 are non-selective cation channels that are highly sensitive to temperature changes, while TRPV5-6 are channels that are highly selective to Ca2+. These cation channels have attracted great interest academically, especially from a pharmacological perspective.
View Article and Find Full Text PDFACS Nano
January 2025
Zhejiang Key Laboratory of Intelligent Cancer Biomarker Discovery and Translation, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou 325035, Zhejiang, P. R. China.
The concept of immunogenic cell death (ICD) induced by chemotherapy as a potential synergistic modality for cancer immunotherapy has been widely discussed. Unfortunately, most chemotherapeutic agents failed to dictate effective ICD responses due to their defects in inducing potent ICD signaling. Here, we report a dual-enzyme-instructed peptide self-assembly platform of (CPT-GFFpY-PLGVRK-Caps) that cooperatively utilizes camptothecin (CPT) and capsaicin (Caps) to promote ICD and engage systemic adaptive immunity for tumor rejection.
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