Department for Air Pollution and Noise, Division of Environmental Medicine, Norwegian Institute of Public Health, Oslo, Norway.
Part Fibre Toxicol. 2008 Nov 13;5:16. doi: 10.1186/1743-8977-5-16.
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-1beta and TNF-alpha were involved in this release from various mono- and co-cultures of monocytes, pneumocytes and endothelial cells.
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-alpha and the IL-1 receptor antagonist revealed that release of IL-1beta, and not TNF-alpha, 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-1beta 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.
IL-1beta 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-1beta 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.
吸入结晶二氧化硅颗粒会引起人类炎症和纤维化的发展。本研究的目的是研究结晶二氧化硅对纤维化和血管生成相关介质 FGF-2 和促炎介质 IL-8 的释放的影响，以及 IL-1β和 TNF-α如何参与来自单核细胞、肺细胞和内皮细胞的各种单核细胞和共培养物中这些介质的释放。
二氧化硅暴露诱导单核细胞和肺细胞单独释放 IL-8 增加，并且二氧化硅暴露于肺细胞时培养基中的 FGF-2 水平增加。内皮细胞的非接触共培养增强了这两种反应。FGF-2 的释放似乎随着二氧化硅诱导的肺细胞数量减少而增加。与非接触培养相比，与单核细胞接触的肺细胞培养物中 IL-8 和 FGF-2 的释放部分受到抑制。用抗 TNF-α和 IL-1 受体拮抗剂处理表明，IL-1β的释放，而不是 TNF-α的释放，在共培养物中主导 IL-8 释放的调节。对于 FGF-2 的释放，IL-1ra 没有作用。然而，外源性 IL-1β降低了 FGF-2 水平，强烈升高了 FGF-2 结合蛋白 PTX3，并阻止了二氧化硅诱导的肺细胞数量减少。
IL-1β似乎在不同的肺细胞培养物中参与二氧化硅诱导的 IL-8 和 FGF-2 的释放。虽然二氧化硅诱导的 IL-8 释放是通过 IL-1 受体介导的机制调节的，但 IL-1β仅通过抵消肺细胞丢失间接影响二氧化硅诱导的 FGF-2 释放。此外，涉及内皮细胞的共培养物中增强的 IL-8 和 FGF-2 反应表明不同细胞类型之间相互作用的重要性，并且可能表明这两种介质在血管生成或纤维化过程中都很重要。
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