Effects of silica dust from silica agglomerates countertops in cellular signalling pathways

Silicosis caused by handling silica agglomerates is an emerging disease. Elucidation of the pathways involved in the origin of the disease could be of great help in finding new potential therapeutic strategies. <bold>Aim</bold>: To analyse some cellular signalling pathways involved in the initial processes of the activation of the inflammatory cells by silica agglomerate dust. <bold>Methods:</bold> Human cell lines from alveolar epithelium (A549) and pleural monocytes (U937) have been cultured and treated with dust from different countertop compositions, named M2, M5, M6 and M7 (Part Fibre Toxicol 18,41(2021)). Additionally, U937 cells were co-cultured with A549 to study the effect of dust-activated macrophages on a lung-derived epithelial cell line. Protein levels were detected by Western blotting. <bold>Results:</bold> A549 cells, in co-culture with dust-activated U937, showed a significant increase of vimentin and α- SMA, markers of the Epithelial-Mesenchymal-Transition (EMT) with M2 and M5 dust. NLRP3, as an inflammasome activation marker, was augmented with M6, and no significant activation was observed for P38MAPK pathway. Also, a significant increase in the expression of STAT-3, AKT and SRC was observed with exposure to M2 and M5 dust, but no differences were observed for the phosphorylated forms of those proteins. The same was observed for ERK42 and ERK44 but the increase was only significant for M5 dust. <bold>Conclusions:</bold> Some cellular pathways are differentially activated with dust from different manufactured countertops. It has been postulated that other chemical components, apart from silica, may influence the development and aggressiveness of the disease. Grants: ISCIII:PI19/01064,FPS 201800016448‐TRA