Open AccessPannexin3 inhibits TNF ‐α‐induced inflammatory response by suppressing NF ‐κB signalling pathway in human dental pulp cells
Author(s) -
Song Fangfang,
Sun Hualing,
Wang Yake,
Yang Hongye,
Huang Liyuan,
Fu Dongjie,
Gan Jing,
Huang Cui
Publication year - 2017
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.12988
Subject(s) - inflammation , proinflammatory cytokine , western blot , tumor necrosis factor alpha , nf κb , gene knockdown , chemistry , pharmacology , pannexin , pulp (tooth) , medicine , immunology , dentistry , apoptosis , biochemistry , intracellular , gap junction , connexin , gene
Human dental pulp cells ( HDPC s) 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 HDPC s 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 MG 132, a proteasome inhibitor. Unlike MG 132, 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 HDPC s. TNF ‐α‐induced pro‐inflammatory cytokines, interleukin ( IL )‐1β and IL ‐6, were significantly lessened when Panx3 was overexpressed in HDPC s. 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.