BACKGROUND 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. RESULTS 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. CONCLUSION 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.

中文翻译：

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在结晶二氧化硅处理的肺细胞共培养物中，IL-1beta 以不同方式参与 IL-8 和 FGF-2 的释放。

背景技术人类吸入结晶二氧化硅颗粒与炎症和纤维化的发展有关。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 释放的影响，以及 IL-1beta 和 TNF-alpha 是如何参与的在这种从单核细胞、肺细胞和内皮细胞的各种单一和共培养物中释放出来的过程中。结果 二氧化硅暴露导致单核细胞和肺细胞单独释放 IL-8 增加，并且在肺细胞暴露于二氧化硅后，培养基中的 FGF-2 水平增加。在与内皮细胞的非接触共培养物中，这两种反应都得到增强。FGF-2 的释放似乎随着二氧化硅诱导的肺细胞数量的减少而增加。与非接触培养物相比，在肺细胞与单核细胞接触的培养物中，IL-8 和 FGF-2 的释放受到部分抑制。用抗 TNF-α 和 IL-1 受体拮抗剂治疗表明，单核细胞中 IL-1β 而非 TNF-α 的释放主导了共培养物中 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-1beta 降低了 FGF-2 水平，强烈提升了 FGF-2 结合蛋白 PTX3，并阻止了二氧化硅诱导的肺细胞数量的减少。结论 IL-1beta 似乎在不同肺细胞培养物中以不同方式参与二氧化硅诱导的 IL-8 和 FGF-2 释放。而二氧化硅诱导的 IL-8 释放是通过 IL-1 受体介导的机制调节的，IL-1beta 仅被建议通过抵消肺细胞损失来间接影响二氧化硅诱导的 FGF-2 释放。此外，在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生成过程中都很重要。