2-hydroxyethyl methacrylate-derived reactive oxygen species stimulate ATP release via TRPA1 in human dental pulp cells

Orimoto, Ai; Kitamura, Chiaki; Ono, Katsushige

doi:10.1038/s41598-022-16559-8

Cited by 3 publications

(1 citation statement)

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“…H 2 O 2 is generally applied in tooth bleaching procedures, and it can damage pulpal cells and induce the expression of inflammatory mediators, as well as TRPA1 channels (Chen et al, 2021b; Cintra et al, 2013; Soares et al, 2015). 2‐Hydroxyethyl methacrylate, a substance used in dental restorations, was also suggested to activate TRPA1 channels via ROS in an hDPC cell line (Orimoto et al, 2022). Our results have shown that inflamed pulp can be even more sensitive to ROS due to TRPA1 up‐regulation.…”

Section: Discussionmentioning

confidence: 99%

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

Kunka,

Lisztes,

Bohács

et al. 2024

British J Pharmacology

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Background and PurposePulpitis 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 ApproachInflammatory 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 ResultsTranscripts 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 ImplicationsPharmacological blockade of TRPA1 channels may be a promising therapeutic approach to alleviate pulpitis and inflammation‐associated pulpal damage.

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Section: Discussionmentioning

confidence: 99%

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

Kunka,

Lisztes,

Bohács

et al. 2024

British J Pharmacology

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Transient Receptor Potential Ankyrin 1 (TRPA1) Mediated LPS‐Induced Inflammation in Periodontal Ligament Stem Cells by Inhibiting the Phosphorylation of JNK

Wang,

Chen,

Gao

et al. 2024

Stem Cells International

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Transient receptor potential ankyrin 1 (TRPA1) molecule is an important type of transient receptor potential (TRP) cation channels, which can cause extracellular Ca2+ to flow into cells after activation. TRPA1 plays an important role in acute and chronic pain, inflammation, kidney disease, cough and asthma, osteoarthritis, cardiovascular disease, obesity, diabetes, and other diseases. In this study, the expression of interleukin (IL)‐1β, IL‐6, and IL‐8 in periodontal ligament stem cells (PDLSCs) treated by lipopolysaccharide (LPS) and the effect of LPS on PDLSCS proliferation were detected. Meanwhile, the change in TRPA1 expression in PDLSCs treated by LPS was also assessed. By knocking down the expression of TRPA1 and using the TRPA1 antagonist HC‐030031, the expression of IL‐1β, IL‐6, and IL‐8 in PDLSCs treated by LPS was downregulated. After LPS stimulation, the proliferation ability of PDLSCs decreased, the gene expression and secretion of IL‐1β, IL‐6, and IL‐8 increased and the gene and protein expression of TRPA1 were upregulated. Reducing the expression of TRPA1 can effectively inhibit the increase of gene expression of IL‐1β, IL‐6, and IL‐8 after LPS stimulation, and pretreatment of PDLSCs with HC‐030031 can also achieve the above effect. And research has found that HC‐030031 can inhibit the phosphorylation level of JNK in PDLSCs treated by LPS. The use of JNK inhibitor JNK‐IN‐8 can also reduce the expression of IL‐1β, IL‐6, and IL‐8 in PDLSCs. Finally, this study found LPS could cause the upregulation of TRPA1, and the inhibition of TRPA1 could produce an anti‐inflammatory effect in PDLSCs treated by LPS due to its inhibition of JNK phosphorylation.

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TRPV2 modulates mechanically Induced ATP Release from Human bronchial epithelial cells

Dunne,

Martin,

Sergeant

et al. 2024

Respir Res

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Repetitive bouts of coughing expose the large airways to significant cycles of shear stress. This leads to the release of alarmins and the tussive agent adenosine triphosphate (ATP) which may be modulated by the activity of ion channels present in the human airway. This study aimed to investigate the role of the transient receptor potential subfamily vanilloid member 2 (TRPV2) channel in mechanically induced ATP release from primary bronchial epithelial cells (PBECs).PBECs were obtained from individuals undergoing bronchoscopy. They were cultured in vitro and exposed to mechanical stress in the form of compressive and fluid shear stress (CFSS) or fluid shear stress (FSS) alone at various intensities. ATP release was measured using a luciferin–luciferase assay. Functional TRPV2 protein expression in human PBECs was investigated by confocal calcium imaging. The role of TRPV2 inhibition on FSS-induced ATP release was investigated using the TRPV2 inhibitor tranilast or siRNA knockdown of TRPV2. TRPV2 protein expression in human lung tissue was also determined by immunohistochemistry.ATP release was significantly increased in PBECs subjected to CFSS compared with control (unstimulated) PBECs (N = 3, ***P < 0.001). PBECs expressed functional TRPV2 channels. TRPV2 protein was also detected in fixed human lung tissue. ATP release from FFS stimulated PBECs was decreased by the TRPV2 inhibitor tranilast (N = 3, **P < 0.01) (vehicle: 159 ± 17.49 nM, tranilast: 25.08 ± 5.1 nM) or by TRPV2 siRNA knockdown (N = 3, *P < 0.05) (vehicle: 197 ± 24.52 nM, siRNA: 119 ± 26.85 nM).In conclusion, TRPV2 is expressed in the human airway and modulates ATP release from mechanically stimulated PBECs.

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2-hydroxyethyl methacrylate-derived reactive oxygen species stimulate ATP release via TRPA1 in human dental pulp cells

Cited by 3 publications

References 36 publications

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

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

Transient Receptor Potential Ankyrin 1 (TRPA1) Mediated LPS‐Induced Inflammation in Periodontal Ligament Stem Cells by Inhibiting the Phosphorylation of JNK

TRPV2 modulates mechanically Induced ATP Release from Human bronchial epithelial cells

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