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Int Endod J. 2015 Jul;48(7):705-16. doi: 10.1111/iej.12396. Epub 2014 Nov 5.

TNF-α and LPS activate angiogenesis via VEGF and SIRT1 signalling in human dental pulp cells.

Author information

1
Department of Prosthodontics, Dongatn Sacred Heart Hospital, Hallym University, Dongtan, Korea.
2
Department of Oral Medicine, School of Dentistry, Kyung Hee University, Seoul, Korea.
3
Department of Oral and Maxillofacial Pathology, Research Center for Tooth and Periodontal Regeneration (MRC), School of Dentistry, Kyung Hee University, Seoul, Korea.
4
Department of Conservative Dentistry, School of Dentistry, Kyung Hee University, Seoul, Korea.

Abstract

AIM:

To assess whether SIRT1 and VEGF are responsible for tumour necrosis factor-α (TNF-α) and lipopolysaccharide (LPS)-induced angiogenesis and to examine the molecular mechanism(s) of action in human dental pulp cells (HDPCs).

METHODOLOGY:

Immortalized HDPCs obtained from Prof. Takashi Takata (Hiroshima University, Japan) were treated with LPS (1 μg mL(-1) ) and TNF-α (10 ng mL(-1) ) for 24 h. mRNA and protein levels were examined by RT-PCR and Western blotting, respectively. Migration and tube formation were examined in human umbilical vein endothelial cells (HUVECs). The data were analysed by one-way anova. Statistical analysis was performed at α = 0.05.

RESULTS:

LPS and TNF-α upregulated VEGF and SIRT1 mRNA and protein levels. Inhibition of SIRT1 activity by sirtinol and SIRT1 siRNA or inhibition of the VEGF receptor by CBO-P11 significantly attenuated LPS + TNF-α-stimulated MMPs production in HDPCs, as well as migration and tube formation in HUVECs (P < 0.05). Furthermore, sirtinol, SIRT1 siRNA and CBO-P11 attenuated phosphorylation of Akt, extracellular signal-regulated kinase (ERK), p38 and c-Jun N-terminal kinase (JNK) and the nuclear translocation of NF-κB p65. Pre-treatment with inhibitors of p38, ERK, JNK, PI3K and NF-κB decreased LPS + TNF-α-induced VEGF and SIRT1 expression, MMPs activity in HDPCs and angiogenesis (P < 0.05) in HUVECs.

CONCLUSIONS:

TNF-α and LPS led to upregulation of VEGF and SIRT1, and subsequent upregulation of MMP-2 and MMP-9 production, and promote angiogenesis via pathways involving PI3K, p38, ERK, JNK and NF-κB. The results suggest that inhibition of SIRT1 and VEGF might attenuate pro-inflammatory mediator-induced pulpal disease.

KEYWORDS:

angiogenesis; human dental pulp cells; lipopolysaccharide; silent information regulator protein 1; tumour necrosis factor-α; vascular endothelial growth factor

PMID:
25311745
DOI:
10.1111/iej.12396
[Indexed for MEDLINE]

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