Abstract
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.
Highlights
Dental pulp inflammation is a widespread public problem and is commonly a sequel to caries or trauma [1]
Dental pulp tissues were isolated from healthy control individuals and dental pulpitis patients, and their expressions of Pannexin 3 (Panx3) and TNF-a were detected by immunohistochemistry staining (Fig. 1A)
Focusing on the effect of Panx3 in dental pulp inflammation, we showed that Panx3 was decreased in inflamed dental pulp tissues and Panx3 level was down-regulated by TNF-a, indicating that Panx3 might participate in pro-inflammatory response of human dental pulp cells (HDPCs)
Summary
Dental pulp inflammation is a widespread public problem and is commonly a sequel to caries or trauma [1]. In clinical setting, such inflammation always causes severe pain, of which level has been anecdotally considered as “the highest level possible” [2, 3], and if kept uncontrolled, it may even result in fatal systemic inflammatory disorders [3, 4]. The mainstream studies have primarily emphasized on the roles of immune cells [5, 6], such as dendritic cells, macrophages and lymphocytes. TNF-a, which has been documented as an objective marker of early inflammation, plays important roles in the inflammatory response [10,11,12,13]
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