Pannexin3 inhibits TNF-α-induced inflammatory response by suppressing NF-κB signalling pathway in human dental pulp cells.
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.
The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of Education (KLOBM), School & Hospital of Stomatology, Wuhan University, Wuhan, Hubei, China.
Fangfang
F
Song
The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of Education (KLOBM), School & Hospital of Stomatology, Wuhan University, Wuhan, Hubei, China.
Hualing
H
Sun
The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of Education (KLOBM), School & Hospital of Stomatology, Wuhan University, Wuhan, Hubei, China.
Yake
Y
Wang
The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of Education (KLOBM), School & Hospital of Stomatology, Wuhan University, Wuhan, Hubei, China.
Hongye
H
Yang
The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of Education (KLOBM), School & Hospital of Stomatology, Wuhan University, Wuhan, Hubei, China.
Liyuan
L
Huang
Department of Stomatology, Renmin Hospital of Wuhan University, Wuhan, Hubei, China.
Dongjie
D
Fu
The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of Education (KLOBM), School & Hospital of Stomatology, Wuhan University, Wuhan, Hubei, China.
Jing
J
Gan
The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of Education (KLOBM), School & Hospital of Stomatology, Wuhan University, Wuhan, Hubei, China.
Cui
C
Huang
D000293:Adolescent; D000328:Adult; D000818:Animals; D002478:Cells, Cultured; D017630:Connexins / Q000378:metabolism*; D003782:Dental Pulp / Q000378:metabolism*; D005260:Female; D006801:Humans; D007249:Inflammation / Q000378:metabolism*; D018836:Inflammation Mediators / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D016328:NF-kappa B / Q000378:metabolism*; D051381:Rats; D015398:Signal Transduction / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D055815:Young Adult
D017630:Connexins; D018836:Inflammation Mediators; D053583:Interleukin-1beta; D015850:Interleukin-6; D016328:NF-kappa B; C492766:PANX3 protein, human; D014409:Tumor Necrosis Factor-alpha
NF-κB; Pannexin3; TNF-α; human dental pulp cells; proteasome; pulpitis
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