ArticlePloS one2008
Human keratinocytes are vanilloid resistant.
Article in PloS one, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
What it found
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Who cites it
29 citing papers in PubMed, 62 citations in OpenAlex.
- Tooth Pulp Afferents and Transient Receptor Potential (TRP) Ion Channels as Key Regulators of Pulp Homeostasis, Inflammation, and Pain.International journal of molecular sciences · 2025Review
- Antibody selection and automated quantification of TRPV1 immunofluorescence on human skin.Scientific reports · 2024Article
- Review
- Convergence of peptidergic and non-peptidergic protein markers in the human dorsal root ganglion and spinal dorsal horn.The Journal of comparative neurology · 2021Article
- TRPV1: Role in Skin and Skin Diseases and Potential Target for Improving Wound Healing.International journal of molecular sciences · 2021Review
- Fight fire with fire: Neurobiology of capsaicin-induced analgesia for chronic pain.Pharmacology & therapeutics · 2021Review
- Stability, permeation, and cytotoxicity reduction of capsicum extract nanoparticles loaded hydrogel containing wax gourd extract.Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society · 2020Article
- Inflammation, Cancer and Immunity-Implication of TRPV1 Channel.Frontiers in oncology · 2019Review
- Protective effects of glycerol and xylitol in keratinocytes exposed to hyperosmotic stress.Clinical, cosmetic and investigational dermatology · 2019Article
- Citron Essential Oils Alleviate the Mediators Related to Rosacea Pathophysiology in Epidermal Keratinocytes.Annals of dermatology · 2018Article
- Itch induced by peripheral mu opioid receptors is dependent on TRPV1-expressing neurons and alleviated by channel activation.Scientific reports · 2018Article
- Human podocytes express functional thermosensitive TRPV channels.British journal of pharmacology · 2017Article
- Diet and rosacea: the role of dietary change in the management of rosacea.Dermatology practical & conceptual · 2017Review
- Targeting breast cancer cells by MRS1477, a positive allosteric modulator of TRPV1 channels.PloS one · 2017Article
- Molecular Surgery Concept from Bench to Bedside: A Focus on TRPV1+ Pain-Sensing Neurons.Frontiers in physiology · 2017Review
- TRPs in Pain Sensation.Frontiers in physiology · 2017Review
- RNA-Seq Analysis of Human Trigeminal and Dorsal Root Ganglia with a Focus on Chemoreceptors.PloS one · 2015Article
- TRP channels in the skin.British journal of pharmacology · 2014Review
- Upregulation of the transient receptor potential ankyrin 1 ion channel in the inflamed human and mouse colon and its protective roles.PloS one · 2014Article
- Aquagenic keratoderma. Two new case reports and a new hypothesis.Indian dermatology online journal · 2014Article
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundUse of capsaicin or resiniferatoxin (RTX) as analgesics is an attractive therapeutic option. RTX opens the cation channel inflammatory pain/vanilloid receptor type 1 (TRPV1) permanently and selectively removes nociceptive neurons by Ca(2+)-cytotoxicity. Paradoxically, not only nociceptors, but non-neuronal cells, including keratinocytes express full length TRPV1 mRNA, while patient dogs and experimental animals that underwent topical treatment or anatomically targeted molecular surgery have shown neither obvious behavioral, nor pathological side effects.
methodsTo address this paradox, we assessed the vanilloid sensitivity of the HaCaT human keratinocyte cell line and primary keratinocytes from skin biopsies.
resultsAlthough both cell types express TRPV1 mRNA, neither responded to vanilloids with Ca(2+)-cytotoxicity. Only ectopic overproduction of TRPV1 rendered HaCaT cells sensitive to low doses (1-50 nM) of vanilloids. The TRPV1-mediated and non-receptor specific Ca(2+)-cytotoxicity ([RTX]>15 microM) could clearly be distinguished, thus keratinocytes were indeed resistant to vanilloid-induced, TRPV1-mediated Ca(2+)-entry. Having a wider therapeutic window than capsaicin, RTX was effective in subnanomolar range, but even micromolar concentrations could not kill human keratinocytes. Keratinocytes showed orders of magnitudes lower TRPV1 mRNA level than sensory ganglions, the bona fide therapeutic targets in human pain management. In addition to TRPV1, TRPV1b, a dominant negative splice variant was also noted in keratinocytes.
conclusionTRPV1B expression, together with low TRPV1 expression, may explain the vanilloid paradox: even genuinely TRPV1 mRNA positive cells can be spared with therapeutic (up to micromolar) doses of RTX. This additional safety information might be useful for planning future human clinical trials.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.