Abstract
The inhalation of combustion-derived nanoparticles leads to adverse health effects in the airways. In this context the induction of membrane-coupled signalling is considered as causative for changes in tissue homeostasis and pro-inflammatory reactions. The identification of these molecular cell reactions allowed to seek for strategies which interfere with these adverse effects. In the current study, we investigated the structurally different compatible solutes mannosylglycerate (firoin) from thermophilic bacteria and ectoine from halophilic bacteria for their capability to reduce signalling pathways triggered by carbon nanoparticles in target cells in the lung. The pre-treatment of lung epithelial cells with both substances decreased the particle-specific activation of mitogen-activated protein kinases and also the endpoints proliferation and apoptosis. Firoin applied into the lungs of animals, like ectoine, led to a significant reduction of the neutrophilic lung inflammation induced by particle exposure. The pro-inflammatory effect of carbon nanoparticles on human neutrophil granulocytes ex vivo was significantly reduced by both substances via the reduction of the anti-apoptotic membrane-dependent signalling. The data of this study together with earlier studies demonstrate that two structurally non-related compatible solutes are able to prevent pathogenic reactions of the airways to carbon nanoparticles by interfering with signalling events. The findings highlight the preventive or therapeutic potential of compatible solutes for adverse health effects caused by particle exposure of the airways.
Highlights
The inhalation of combustion-derived carbonaceous nanoparticles leads to adverse health effects in the airways including lung cancer, chronic obstructive pulmonary disease, and fibrosis [1,2,3,4]
In studies with human and rat lung epithelial cells we found that pure carbon nanoparticles (CNP) induced adverse endpoints like the upregulation of pro-inflammatory cytokines, apoptosis and proliferation [5, 8]
These endpoints are mediated by separate specific mitogen-activated protein kinases (MAPK) pathways, while Erk1/2 activation is a pre-requisite for proliferation, the phosphorylation of JNK1/2 is specific for CNP-triggered apoptosis
Summary
The inhalation of combustion-derived carbonaceous nanoparticles leads to adverse health effects in the airways including lung cancer, chronic obstructive pulmonary disease, and fibrosis [1,2,3,4]. In studies with human and rat lung epithelial cells we found that pure carbon nanoparticles (CNP) induced adverse endpoints like the upregulation of pro-inflammatory cytokines, apoptosis and proliferation [5, 8]. These endpoints are mediated by separate specific MAPK pathways, while Erk1/2 activation is a pre-requisite for proliferation, the phosphorylation of JNK1/2 is specific for CNP-triggered apoptosis. CNP trigger specific membrane-dependent signalling pathways which reduce the natural apoptosis rates of these immune cells and contribute to the aggravation of the inflammation [9]
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