Abstract
BackgroundDexmedetomidine (Dex) is a highly selective agonist of the α2 adrenergic receptor and a common sedative; however, its anti-inflammatory effect has been studied. In this study, the inhibitory effect of Dex on inflammation in dental pulp cells was assessed. For this, the effect of Dex on inflammation induced by carrageenan (Car) in human dental pulp cells (hDPCs) was evaluated. Car incubation induced a robust inflammatory response in hDPCs as well as activation of PKA–STAT3 and PKC–nuclear factor kappa B (NF-κB) signaling pathways.ResultsDex reduced the expression of inflammatory cytokines in a dose-dependent manner. Meanwhile, the phosphorylation of PKA, PKC, STAT3, and NF-κB as well as the nuclear accumulation of STAT3 and NF-κB were significantly increased in Dex-treated Car-induced hDPCs. Western blotting results also showed that the phosphorylation level of transient receptor potential cation channel subfamily V member 1 (TRPV1) was downregulated as a result of Dex treatment. Furthermore, we found that administration of the TRPV1 agonist capsaicin (Cap) reversed the effects of Dex on proinflammatory cytokines; however, the expression and activation of PKA–STAT3 and PKC–NF-κB signals were not altered owing to Cap administration.ConclusionsThese results indicate that Dex plays a defensive role in dental pulp inflammation by regulating the TRPV1 channel and can be used as a potential target for human dental pulp inflammation intervention.
Highlights
Pulp exposure and injury leads to pulpitis and induces severe inflammation, frequently resulting in persistent pain and referred pain
Expression of proinflammatory cytokines induced by car in human dental pulp cells (hDPCs) To explore hDPC inflammation following Car treatment, the expression of proinflammatory cytokines in hDPCs was assessed. quantitative real-time polymerase chain reaction (qPCR) and Enzyme-linked immunosorbent assay (ELISA) test results revealed that messenger RNA and protein expressions of IL1β, IL-6, and TNF-α in HDPCs after Car treatment were higher than those in the control group (P < 0.01) (Fig. 1a and b)
Car-induced activation of PKA–STAT3 and PKC–nuclear factor kappa B (NF-κB) in induced hDPCs Because the activation of the PKA–STAT3 and PKC–NFκB pathways is crucial for inducing cytokine expression [22, 23] the expression and phosphorylation of PKA, STAT3, PKC, and NF-κB after Car treatment were evaluated. qPCR results suggest that Car upregulates the messenger RNA (mRNA) expressions of STAT3 and NF-κB (P < 0.05), while the PKA and PKC expressions were not altered (Fig. 2a)
Summary
Pulp exposure and injury leads to pulpitis and induces severe inflammation, frequently resulting in persistent pain and referred pain. HDPCs induced by proinflammatory mediators, including tumor necrosis factor alpha (TNF-α) and lipopolysaccharide (LPS), can locally secrete numerous cytokines to attract additional immune cells and initiate and regulate inflammation [8, 9]. The direct effect of inflammatory mediators such as prostaglandins (PGI2 and PGE2) and sympathetic amines (epinephrine and dopamine) on their receptors in the nociceptor membrane can cause sensitization. Dexmedetomidine (Dex) is a highly selective agonist of the α2 adrenergic receptor and a common sedative; its anti-inflammatory effect has been studied. The inhibitory effect of Dex on inflammation in dental pulp cells was assessed. The effect of Dex on inflammation induced by carrageenan (Car) in human dental pulp cells (hDPCs) was evaluated. Car incubation induced a robust inflammatory response in hDPCs as well as activation of PKA–STAT3 and PKC–nuclear factor kappa B (NF-κB) signaling pathways
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