Functional expression of α7 nicotinic acetylcholine receptors in human periodontal ligament fibroblasts and rat periodontal tissues

Abstract

Tobacco smoking is the main risk factor associated with chronic periodontitis, but the mechanisms that underlie this relationship are largely unknown. Recent reports proposed that nicotine plays an important role in tobacco-related morbidity by acting through the nicotinic acetylcholine receptors (nAChRs) expressed by non-neuronal cells. The aim of this study was to investigate whether alpha 7 nAChR was expressed in periodontal tissues and whether it functions by regulating IL-1 beta in the process of periodontitis. In vitro, human periodontal ligament (PDL) cells were cultured with 10(-12) M of nicotine and/or 10(-9) M of alpha-bungarotoxin (alpha-Btx), a alpha 7 nAChR antagonist. The expression of alpha 7 nAChR and IL-1 beta in PDL cells and the effects of nicotine/alpha-Btx administration on their expression were explored. In vivo, an experimental periodontitis rat model was established, and the effects of nicotine/alpha-Btx administration on expression of alpha 7 nAChR and development of periodontitis were evaluated. We found that alpha 7 nAChR was present in human PDL cells and rat periodontal tissues. The expressions of alpha 7 nAChR and IL-1 beta were significantly increased by nicotine administration, whereas alpha-Btx treatment partially suppressed these effects. This study was the first to demonstrate the functional expression of alpha 7 nAChR in human PDL cells and rat periodontal tissues. Our results may be pertinent to a better understanding of the relationships among smoking, nicotine, and periodontitis.

Nicotine Induces the Production of IL-1� and IL-8 via the a7 nAChR/NF-κB Pathway in Human Periodontal Ligament Cells: anin VitroStudy

“…In previous studies, we demonstrated the functional expression of α7 nAChR in human and rat periodontal tissue. Up-regulation of α7 nAChR upon the administration of nicotine could be inhibited by pretreatment with α-BTX, the α7 nAChR antagonist [9], suggesting that nicotine could affect smoking-associated periodontitis via α7 nAChR.…”

Nicotinic Acetylcholine Receptor α7 and β4 Subunits Contribute to Nicotine-Induced Apoptosis in Periodontal Ligament Stem Cells

“…Nicotine is a lipophilic molecule of which the effects on neuronal nicotinic acetylcholine receptors (nAChR) have been primarily focused on its physiologic impact within the confines of the nervous system (Mao et al, 2011). However, many studies have recently found neuronal nAChRs to be expressed on many different non-neuronal cell types throughout the body (Chernyavsky et al, 2005;Resende et al, 2008;Wang et al, 2010;Wessler and Kirkpatrick, 2008). Recently, studies have found that nAChRs can be expressed on oral gingival and periodontal tissues (Nguyen et al, 2000;Wang et al, 2010).…”

“…However, many studies have recently found neuronal nAChRs to be expressed on many different non-neuronal cell types throughout the body (Chernyavsky et al, 2005;Resende et al, 2008;Wang et al, 2010;Wessler and Kirkpatrick, 2008). Recently, studies have found that nAChRs can be expressed on oral gingival and periodontal tissues (Nguyen et al, 2000;Wang et al, 2010). The expression of α7 nAChR in periodontal tissues can initiate the function of the regulation IL-1β in the process of periodontitis (Wang et al, 2010).…”

“…Recently, studies have found that nAChRs can be expressed on oral gingival and periodontal tissues (Nguyen et al, 2000;Wang et al, 2010). The expression of α7 nAChR in periodontal tissues can initiate the function of the regulation IL-1β in the process of periodontitis (Wang et al, 2010). It has been reported that nicotine substantially affects the levels of α5 and α7 nAChR expressions in oral keratinocytes, and it has been suggested that nAChRs have an important pathophysiological effect on determining the consequences of nicotine use on the diseased state (Arredondo et al, 2008).…”

“…A functional nAChR consists of five subunits which may differ (certain combinations of α1-9 and β1-4, γ, δ, and ε subunits) or be identical (α7-9) subunits and diverse subunit composition of nAChRs exhibit very different pharmacological and functional properties in various systems (Portugal and Gould, 2008). Recent studies have demonstrated that nicotinic receptors are expressed in undifferentiated and differentiating non-neuronal cells including embryonic stem cells, immune cells, oral epithelium and periodontal tissues (Chernyavsky et al, 2005;Resende et al, 2008;Wang et al, 2010;Wessler and Kirkpatrick, 2008), suggesting that although nAChRs primarily function as ligand-gated ion channels across synapses, they also influence other cellular activities such as cell to cell communication, sur-vival, and apoptosis in various non-neuronal tissues (Gotti and Clementi, 2004).…”