IL-1beta differently involved in IL-8 and FGF-2 release in crystalline silica-treated lung cell co-cultures

<p>Abstract</p> <p>Background</p> <p>Inhalation of crystalline silica particles is in humans associated with inflammation and development of fibrosis. The aim of the present study was to investigate the effect of crystalline silica on the release of the fibrosis- and angiogenesis-related mediator FGF-2 and the pro-inflammatory mediator IL-8, and how IL-1β and TNF-α were involved in this release from various mono- and co-cultures of monocytes, pneumocytes and endothelial cells.</p> <p>Results</p> <p>Silica exposure induced an increase of IL-8 release from monocytes and from pneumocytes alone, and the FGF-2 level in the medium increased upon silica exposure of pneumocytes. Both the responses were enhanced in non-contact co-cultures with endothelial cells. The FGF-2 release seemed to increase with the silica-induced decrease in the number of pneumocytes. The release of IL-8 and FGF-2 was partially suppressed in cultures with pneumocytes in contact with monocytes compared to non-contact cultures. Treatment with anti-TNF-α and the IL-1 receptor antagonist revealed that release of IL-1β, and not TNF-α, from monocytes dominated the regulation of IL-8 release in co-cultures. For release of FGF-2, IL-1ra was without effect. However, exogenous IL-1β reduced the FGF-2 levels, strongly elevated the FGF-2-binding protein PTX3, and prevented the reduction in the number of pneumocytes induced by silica.</p> <p>Conclusion</p> <p>IL-1β seems to be differently involved in the silica-induced release of IL-8 and FGF-2 in different lung cell cultures. Whereas the silica-induced IL-8 release is regulated via an IL-1-receptor-mediated mechanism, IL-1β is suggested only indirectly to affect the silica-induced FGF-2 release by counteracting pneumocyte loss. Furthermore, the enhanced IL-8 and FGF-2 responses in co-cultures involving endothelial cells show the importance of the interaction between different cell types and may suggest that both these mediators are important in angiogenic or fibrogenic processes.</p

Wood smoke particles from different combustion phases induce similar pro-inflammatory effects in a co-culture of monocyte and pneumocyte cell lines

Background Exposure to particulate matter (PM) has been linked to several adverse cardiopulmonary effects, probably via biological mechanisms involving inflammation. The pro-inflammatory potential of PM depends on the particles’ physical and chemical characteristics, which again depend on the emitting source. Wood combustion is a major source of ambient air pollution in Northern countries during the winter season. The overall aim of this study was therefore to investigate cellular responses to wood smoke particles (WSPs) collected from different phases of the combustion cycle, and from combustion at different temperatures. Results WSPs from different phases of the combustion cycle induced very similar effects on pro-inflammatory mediator release, cytotoxicity and cell number, whereas WSPs from medium-temperature combustion were more cytotoxic than WSPs from high-temperature incomplete combustion. Furthermore, comparisons of effects induced by native WSPs with the corresponding organic extracts and washed particles revealed that the organic fraction was the most important determinant for the WSP-induced effects. However, the responses induced by the organic fraction could generally not be linked to the content of the measured polycyclic aromatic hydrocarbons (PAHs), suggesting that also other organic compounds were involved. Conclusion The toxicity of WSPs seems to a large extent to be determined by stove type and combustion conditions, rather than the phase of the combustion cycle. Notably, this toxicity seems to strongly depend on the organic fraction, and it is probably associated with organic components other than the commonly measured unsubstituted PAHs