Neuronal nicotinic receptors in non-neuronal cells: new mediators of tobacco toxicity?

Conti‐Fine, Bianca M.; Navaneetham, Duraiswamy; Liu, Sijin; Maus, Arno

doi:10.1016/s0014-2999(00)00036-4

Cited by 158 publications

(125 citation statements)

References 81 publications

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“…These ligand-gated ion channels represent the most common homomeric form of nAChRs in the body, and although their expression is highest in the central nervous system and muscle, they have been detected in fetal and adult lungs and in other organs (4). ␣ 7 nAChRs mediate the stimulatory effects of nicotine on matrix expression in lung fibroblasts (22).…”

mentioning

confidence: 99%

Nicotine alters lung branching morphogenesis through the α₇ nicotinic acetylcholine receptor

Wongtrakool

Roser‐Page²,

Rivera³

et al. 2007

American Journal of Physiology-Lung Cellular and Molecular Phys

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There is abundant epidemiological data linking prenatal environmental tobacco smoke with childhood asthma and wheezing, but the underlying molecular and physiological mechanisms that occur in utero to explain this link remain unelucidated. Several studies suggest that nicotine, which traverses the placenta, is a causative agent. Therefore, we studied the effects of nicotine on lung branching morphogenesis using embryonic murine lung explants. We found that the expression of α7 nicotinic acetylcholine receptors, which mediate many of the biological effects of nicotine, is highest in pseudoglandular stage lungs compared with lungs at later stages. We then studied the effects of nicotine in the explant model and found that nicotine stimulated lung branching in a dose-dependent fashion. α-Bungarotoxin, an antagonist of α7 nicotinic acetylcholine receptors, blocked the stimulatory effect of nicotine, whereas GTS-21, a specific agonist, stimulated branching, thereby mimicking the effects of nicotine. Explants deficient in α7 nicotinic acetylcholine receptors did not respond to nicotine. Nicotine also stimulated the growth of the explant. Altogether, these studies suggest that nicotine stimulates lung branching morphogenesis through α7 nicotinic acetylcholine receptors and may contribute to dysanaptic lung growth, which in turn may predispose the host to airway disease in the postnatal period.

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mentioning

confidence: 99%

Nicotine alters lung branching morphogenesis through the α₇ nicotinic acetylcholine receptor

Wongtrakool

Roser‐Page²,

Rivera³

et al. 2007

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…In addition, nonneuronal cells such as monocytes, endothelial cells, and epithelial cells also express nACh receptors. [1][2][3][4] However, the effect of nicotine on immune cells is incompletely characterized and controversial. Some investigators have provided evidence that nicotine promotes inflammation.…”

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confidence: 99%

Nicotine Strongly Activates Dendritic Cell–Mediated Adaptive Immunity

et al. 2003

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Background-Antigen-presenting cells (APCs) such as monocytes and dendritic cells (DCs) stimulate T-cell proliferation and activation in the course of adaptive immunity. This cellular interaction plays a role in the growth of atherosclerotic plaques. Nicotine has been shown to increase the growth of atherosclerotic lesions. Therefore, we investigated whether nicotine can stimulate APCs and their T cell-stimulatory capacity using human monocyte-derived DCs and murine bone marrow-derived DCs as APCs. Methods and Results-Nicotine dose-dependently (10 Ϫ8 to 10 Ϫ4 mol/L) induced DC expression of costimulatory molecules (ie, CD86, CD40), MHC class II, and adhesion molecules (ie, LFA-1, CD54). Moreover, nicotine induced a 7.0-fold increase in secretion of the proinflammatory T H 1 cytokine interleukin-12 by human DCs. These effects were abrogated by the nicotinic receptor antagonist ␣-bungarotoxin and mecamylamine, respectively. The effects of nicotine were mediated in part by the phosphorylation of the PI3 kinase downstream target Akt and the mitogen-activated kinases ERK and p38 MAPK. Nicotine-stimulated APCs had a greater capacity to stimulate T-cell proliferation and cytokine secretion, as documented by mixed lymphocyte reactions and ovalbumin-specific assays with ovalbumin-transgenic DO10.11 mice. In a murine model of atherosclerosis, nicotine significantly enhanced the recruitment of DCs to atherosclerotic lesions in vivo. Conclusions-Nicotine activates DCs and augments their capacity to stimulate T-cell proliferation and cytokine secretion.These effects of nicotine may contribute to its influence on the progression of atherosclerotic lesions.

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“…The a7 subunit is one of the evolutionarily most ancient nAChR subunits, making it likely that a7-nAChR are among the primordial nAChR prototypes . Consistent with this, increasing evidence points to a7-nAChR expression in diverse cell types including neurons, muscle, and tendon (Seguela et al 1993;Corriveau et al 1995;Romano et al 1997;Conti-Fine et al 2000). It is highly likely, therefore, that a7-nAChR play additional important roles yet to be discovered.…”

mentioning

confidence: 77%

Regulation by cycloheximide and lowered temperature of cell‐surface α7‐nicotinic acetylcholine receptor expression on transfected SH‐EP1 cells

Schroeder

Zhao

et al. 2003

Journal of Neurochemistry

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Heterologous expression of functional, nicotinic acetylcholine receptors (nAChR) in mammalian cells has been difficult to achieve or optimize, even for nAChR containing only one kind of subunit. In this study, we determined effects of lowered temperature or of exposure to the protein synthesis inhibitor cycloheximide (CHX) on cell surface expression of homomeric a7-nAChR in transfected SH-EP1 human epithelial cells. We found that incubation of cells for 2 days at 25°C or in the presence of 0.5-2 lg/mL of CHX caused four-or eight-fold increases, respectively, in surface binding sites for 125 I-labeled a-bungarotoxin (I-Bgt). These increases were accompanied by increases in peak whole-cell current responses to nicotinic agonists. Either treatment lowered protein synthesis and cell proliferation, but experiments using puromycin indicated that a reduction in protein synthesis or cell proliferation per se was not sufficient to increase surface binding. I-Bgt binding to whole-cell membrane pools increased in response to either treatment, suggesting that the increase in surface binding was due, at least in part, to an increase in intracellular receptor levels. The cyclophilin inhibitor cyclosporin A reduced surface expression in untreated as well as CHX-or 25°C-treated cells.The results suggest practical means for increasing cell surface and functional expression of a7-nAChR. Although these effects are not simply due to protein synthesis inhibition or reduced cell proliferation, they do involve an increase in intracellular receptor pool size.

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Neuronal nicotinic receptors in non-neuronal cells: new mediators of tobacco toxicity?

Cited by 158 publications

References 81 publications

Nicotine alters lung branching morphogenesis through the α₇ nicotinic acetylcholine receptor

Nicotine alters lung branching morphogenesis through the α₇ nicotinic acetylcholine receptor

Nicotine Strongly Activates Dendritic Cell–Mediated Adaptive Immunity

Regulation by cycloheximide and lowered temperature of cell‐surface α7‐nicotinic acetylcholine receptor expression on transfected SH‐EP1 cells

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Neuronal nicotinic receptors in non-neuronal cells: new mediators of tobacco toxicity?

Cited by 158 publications

References 81 publications

Nicotine alters lung branching morphogenesis through the α7 nicotinic acetylcholine receptor

Nicotine alters lung branching morphogenesis through the α7 nicotinic acetylcholine receptor

Nicotine Strongly Activates Dendritic Cell–Mediated Adaptive Immunity

Regulation by cycloheximide and lowered temperature of cell‐surface α7‐nicotinic acetylcholine receptor expression on transfected SH‐EP1 cells

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Nicotine alters lung branching morphogenesis through the α₇ nicotinic acetylcholine receptor

Nicotine alters lung branching morphogenesis through the α₇ nicotinic acetylcholine receptor