NF-κB Activation in Human Dental Pulp Stem Cells by TNF and LPS

Abstract

Post-natal human dental pulp stem cells (DPSCs) represent a unique precursor population in the dental pulp, which has multipotential and can regenerate a dentin/pulp-like structure. Because the dental pulp is frequently infected by oral bacteria due to dental decay, in this study, we examined whether lipopolysaccharide (LPS) and tumor necrosis factor (TNF) activated the immunologic transcription factor nuclear factor kappa B (NF-kappaB) in DPSCs. We found that both TNF and LPS activated the I-kappa B kinase complex (IKK) in DPSCs to induce the phosphorylation and degradation of IkappaBalpha, resulting in the nuclear translocation of NF-kappaB. Consistently, both TNF and LPS rapidly induced the expression of the NF-kappaB-dependent gene interleukin-8 (IL-8). However, unlike in monocytes, we found that LPS could not induce the phosphorylation of the NF-kappaB active subunit p65 in DPSCs. In summary, our studies suggest that DPSCs may be involved in immune responses during pulpal infection through activating NF-kappaB.

A Dominant Function of IKK/NF-κB Signaling in Global Lipopolysaccharide-induced Gene Expression

“…NF-B consists of homo-and heterodimeric complexes of the Rel family proteins, including p50, p52, p65/RelA, c-Rel, and RelB. In mammalian cells, the most widely distributed B-binding activity is a heterodimer of p50 and p65/RelA proteins, in which the p65/RelA subunit has potent transactivation activity (17)(18)(19). The IKK complex is critical for NF-B activation induced by LPS and proinflammatory cytokines.…”

“…The IKK complex is critical for NF-B activation induced by LPS and proinflammatory cytokines. The IKK complex is mainly composed of two catalytic subunits, IKK␣ and IKK␤, and IKK␥ (also known as NF-B essential modulator), a scaffold molecule without catalytic activity (17)(18)(19)(20).…”

Expression of the stem cell factor in fibroblasts, endothelial cells, and macrophages in periapical tissues in human chronic periapical diseases

“…LPS in infected pulp tissues of pulp canal could activate LYMs and FBs producing pro-inflammatory cytokines such as TNF and IL-1 (Chang et al, 2005). Some studies have suggested that FBs could be activated to secret inflammatory cytokines, such as NLRP3 and IL-33, after stimulation of inflammation and participate in infiltration, cell transport, and tissues fibrosis in the tissue repair process (Liu and Liu, 2013;Sipert et al, 2014;Velickovic et al, 2016).…”

Oral epithelial barrier function and the role of nuclear factor kappa-? pathway in the pathogenesis of aphthous ulceration

“…TLR activation results in proinflammatory cytokine secretions such as interleukin-1, tumor necrosis factor-alpha, interleukin-8, interleukin-10, and interferons (27,28). Different types of TLRs recognize different antigenic substances, and the specific location of TLR specify the form of the ensuing immuno-inflammatory reaction.…”

“…The mucosal reaction to pathogenic bacteria or permeated antigens also activates the postreceptor NF-κB pathway which is the main pathway of adaptive immunity (13,27). A growing number of studies demonstrate that aberrant NF-κB signaling is critical in the development of various inflammatory diseases (13,14,28,29). NF-κB pathway may be activated by Toll-like receptors/pathogen signals, and proinflammatory cytokins (29).…”