2. Academic Validation
  3. TRPA1 up-regulation mediates oxidative stress in a pulpitis model in vitro

TRPA1 up-regulation mediates oxidative stress in a pulpitis model in vitro

  • Br J Pharmacol. 2024 May 14. doi: 10.1111/bph.16386.
Árpád Kunka 1 2 3 4,  Erika Lisztes 1,  Judit Bohács 1 3 5,  Márk Racskó 1 3,  Balázs Kelemen 1,  Gabriella Kovalecz 6,  Etelka D Tóth 4,  Csaba Hegedűs 7,  Kinga Bágyi 5,  Rita Marincsák 5,  Balázs István Tóth 1
Affiliations

Affiliations

  • 1 Department of Physiology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
  • 2 Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, University of Debrecen, Debrecen, Hungary.
  • 3 Doctoral School of Molecular Medicine, University of Debrecen, Debrecen, Hungary.
  • 4 Department of Dentoalveolar Surgery, Faculty of Dentistry, University of Debrecen, Debrecen, Hungary.
  • 5 Department of Operative Dentistry and Endodontics, Faculty of Dentistry, University of Debrecen, Debrecen, Hungary.
  • 6 Department of Pediatric and Preventive Dentistry, Faculty of Dentistry, University of Debrecen, Debrecen, Hungary.
  • 7 Department of Biomaterials and Prosthetic Dentistry, Faculty of Dentistry, University of Debrecen, Debrecen, Hungary.
PMID: 38744683 DOI: 10.1111/bph.16386
Abstract

Background and purpose: Pulpitis is associated with tooth hypersensitivity and results in pulpal damage. Thermosensitive transient receptor potential (TRP) ion channels expressed in the dental pulp may be key transducers of inflammation and nociception. We aimed at investigating the expression and role of thermo-TRPs in primary human dental pulp cells (hDPCs) in normal and inflammatory conditions.

Experimental approach: Inflammatory conditions were induced in hDPC cultures by applying polyinosinic:polycytidylic acid (poly(I:C)). Gene expression and pro-inflammatory cytokine release were measured by RT-qPCR and ELISA. Functions of TRPA1 channels were investigated by monitoring changes in intracellular CA2+ concentration. Mitochondrial superoxide production was measured using a fluorescent substrate. Cellular viability was assessed by measuring the activity of mitochondrial dehydrogenases and cytoplasmic esterases. TRPA1 activity was modified by agonists, antagonists, and gene silencing.

Key results: Transcripts of TRPV1, TRPV2, TRPV4, TRPC5, and TRPA1 were highly expressed in control hDPCs, whereas TRPV3, TRPM2, and TRPM3 expressions were much lower, and TRPM8 was not detected. Poly(I:C) markedly up-regulated TRPA1 but not other thermo-TRPs. TRPA1 agonist-induced CA2+ signals were highly potentiated in inflammatory conditions. Poly(I:C)-treated cells displayed increased CA2+ responses to H2O2, which was abolished by TRPA1 antagonists. Inflammatory conditions induced oxidative stress, stimulated mitochondrial superoxide production, resulted in mitochondrial damage, and decreased cellular viability of hDPCs. This inflammatory cellular damage was partly prevented by the co-application of TRPA1 antagonist or TRPA1 silencing.

Conclusion and implications: Pharmacological blockade of TRPA1 channels may be a promising therapeutic approach to alleviate pulpitis and inflammation-associated pulpal damage.

Keywords

TRPA1; dental pulp; endodontics; immunopharmacology; inflammation; reactive oxygen species; transient receptor potential channels.

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