Irreversible but not reversible pulpitis is associated with up‐regulation of tumour necrosis factor‐alpha gene expression in human pulp

Κόκκας, Ανδρέας; Goulas, A.; Varsamidis, K.; Mirtsou, Vassiliki; Tziafas, Dimitrios

doi:10.1111/j.1365-2591.2007.01215.x

Cited by 73 publications

(64 citation statements)

References 23 publications

(49 reference statements)

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“…During the treatment of a deep carious lesion, a clinician must decide whether the pulpal inflammation is reversible or irreversible based on subjective findings (4), and therefore objective analysis of pulpal cytokine levels can provide useful information about pulpal pathology. Several cytokines have been suggested to be indicators of inflammation (8,(10)(11). In the present study, comparison of the cytokine levels in mechanically and cariously exposed pulp was able to provide a clearer picture of pulp status at the time of treatment.…”

Section: Discussionmentioning

confidence: 57%

Comparative evaluation of pro-inflammatory cytokine levels in pulpotomized primary molars

et al. 2015

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The present in vivo study was performed to investigate the levels of the pro-inflammatory cytokines, interleukin (IL)-1α, IL-6, and IL-8, in primary molars for which pulpotomy was clinically indicated, and to evaluate the success rates of three different pulpotomy agents employed for cariously (CExp) or mechanically exposed (MExp) primary molars. Forty-seven primary molars were classified as MExp or CExp according to the type of pulpal exposure. Pulp tissue was harvested and analyzed using enzymelinked immunosorbent assay (ELISA). Subsequently, three pulpotomy agents-calcium hydroxide (CH), mineral trioxide aggregate (MTA), and formocresol (FC)-were applied randomly, and the outcome was observed radiographically for 18 months. Levels of IL-6 and IL-8 were significantly higher in CExp pulp than in MExp pulp (P < 0.05). In the CH pulpotomy group, MExp teeth showed a higher success rate than CExp teeth. There was no significant difference in success rate between MExp and CExp teeth in both the FC and MTA groups. The levels of IL-6 and IL-8 have the potential to become indicators of pulp status and can be monitored by researchers to make the prognosis of vital pulp therapies less uncertain. As MTA and FC yielded higher rates of success than CH in CExp teeth, the choice of pulpotomy agent appears to be important in this context. (J Oral Sci 57, 145-150, 2015)

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Section: Discussionmentioning

confidence: 57%

Comparative evaluation of pro-inflammatory cytokine levels in pulpotomized primary molars

et al. 2015

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“…As might be expected, our experiments showed that TNF‐α depressed the expression of Panx3 in a dose‐dependent manner. TNF‐α, both trauma and bacteria could induce its secretion, act as a pro‐inflammatory cytokine and aggravate inflammatory response, then ultimately initiate dental pulp inflammation and pain 10, 11, 12, 13, 24. Previous studies have reported that TNF‐α could suppress the expression of several hemichannels in various cell types 25, 26, 27.…”

Section: Discussionmentioning

confidence: 99%

Pannexin3 inhibits TNF‐α‐induced inflammatory response by suppressing NF‐κB signalling pathway in human dental pulp cells

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Wang

et al. 2016

J Cellular Molecular Medi

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Human dental pulp cells (HDPCs) play a crucial role in dental pulp inflammation. Pannexin 3 (Panx3), a member of Panxs (Pannexins), has been recently found to be involved in inflammation. However, the mechanism of Panx3 in human dental pulp inflammation remains unclear. In this study, the role of Panx3 in inflammatory response was firstly explored, and its potential mechanism was proposed. Immunohistochemical staining showed that Panx3 levels were diminished in inflamed human and rat dental pulp tissues. In vitro, Panx3 expression was significantly down‐regulated in HDPCs following a TNF‐α challenge in a concentration‐dependent way, which reached the lowest level at 10 ng/ml of TNF‐α. Such decrease could be reversed by MG132, a proteasome inhibitor. Unlike MG132, BAY 11‐7082, a NF‐κB inhibitor, even reinforced the inhibitory effect of TNF‐α. Quantitative real‐time PCR (qRT‐PCR) and enzyme‐linked immunosorbent assay (ELISA) were used to investigate the role of Panx3 in inflammatory response of HDPCs. TNF‐α‐induced pro‐inflammatory cytokines, interleukin (IL)‐1β and IL‐6, were significantly lessened when Panx3 was overexpressed in HDPCs. Conversely, Panx3 knockdown exacerbated the expression of pro‐inflammatory cytokines. Moreover, Western blot, dual‐luciferase reporter assay, immunofluorescence staining, qRT‐PCR and ELISA results showed that Panx3 participated in dental pulp inflammation in a NF‐κB‐dependent manner. These findings suggested that Panx3 has a defensive role in dental pulp inflammation, serving as a potential target to be exploited for the intervention of human dental pulp inflammation.

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“…Increased levels of TNF-α have been detected in patients with pulpitis (Pezelj-Ribaric et al 2002;Kokkas et al 2007). We first sought to reaffirm whether patients with tooth decay exhibit increased expression of TNF-α.…”

Section: Development Of a Mouse Model For Conditional Overexpression mentioning

confidence: 99%

“…Elevated levels of TNF-α have often been detected in the serum and tissues of patients with severe infections or autoimmune disorders. For example, upregulation of TNF-α has been discovered in pulpal tissues from teeth with irreversible pulpitis (Pezelj-Ribaric et al 2002;Kokkas et al 2007) and in exudates of teeth with apical periodontitis (Safavi and Rossomando 1991). In addition to being proinflammatory, TNF-α may act directly on nociceptive neurons to increase pain sensitivity.…”

Section: Introductionmentioning

confidence: 99%

Conditional TNF-α Overexpression in the Tooth and Alveolar Bone Results in Painful Pulpitis and Osteitis

et al. 2015

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Tumor necrosis factor-α (TNF-α) is a proalgesic cytokine that is commonly expressed following tissue injury. TNF-α expression not only promotes inflammation but can also lead to pain hypersensitivity in nociceptors. With the established link between TNF-α and inflammatory pain, we identified its increased expression in the teeth of patients affected with caries and pulpitis. We generated a transgenic mouse model (TNF-α glo ) that could be used to conditionally overexpress TNF-α. These mice were bred with a dentin matrix protein 1 (DMP1)-Cre line for overexpression of TNF-α in both the tooth pulp and bone to study oral pain that would result from subsequent development of pulpitis and bone loss. The resulting DMP1/TNF-α glo mice show inflammation in the tooth pulp that resembles pulpitis while also displaying periodontal bone loss. Inflammatory infiltrates and enlarged blood vessels were observed in the tooth pulp. Pulpitis and osteitis affected the nociceptive neurons innervating the orofacial region by causing increased expression of inflammatory cytokines within the trigeminal ganglia. With this new mouse model morphologically mimicking pulpitis and osteitis, we tested it for signs of oral pain with an oral function assay (dolognawmeter). This assay/device records the time required by a mouse to complete a discrete gnawing task. The duration of gnawing required by the DMP1/TNF-α glo mice to complete the task was greater than that for the controls; extended gnaw time in a dolognawmeter indicates reduced orofacial function. With the DMP1/TNF-α glo mice, we have shown that TNF-α expression alone can produce inflammation similar to pulpitis and osteitis and that this mouse model can be used to study dental inflammatory pain.

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Irreversible but not reversible pulpitis is associated with up‐regulation of tumour necrosis factor‐alpha gene expression in human pulp

Abstract: Kokkas AB, Goulas A, Varsamidis K, Mirtsou V, Tziafas D.Irreversible but not reversible pulpitis is associated with up-regulation of tumour necrosis factor-alpha gene expression in human pulp.

Cited by 73 publications

References 23 publications

Comparative evaluation of pro-inflammatory cytokine levels in pulpotomized primary molars

Comparative evaluation of pro-inflammatory cytokine levels in pulpotomized primary molars

Pannexin3 inhibits TNF‐α‐induced inflammatory response by suppressing NF‐κB signalling pathway in human dental pulp cells

Conditional TNF-α Overexpression in the Tooth and Alveolar Bone Results in Painful Pulpitis and Osteitis

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