NF-[kappa]B dependent and independent mechanisms of quartz-induced proinflammatory activation of lung epithelial cells

In the initiation and progression of pulmonary inflammation, macrophages have classically been considered as a crucial cell type. However, evidence for the role of epithelial type II cells in pulmonary inflammation has been accumulating. In the current study, a combined in vivo and in vitro approach has been employed to investigate the mechanisms of quartz-induced proinflammatory activation of lung epithelial cells. In vivo, enhanced expression of the inflammation- and oxidative stress-related genes HO-1 and iNOS was found on the mRNA level in rat lungs after instillation with DQ12 respirable quartz. Activation of the classical NF-[kappa]B pathway in macrophages and type II pneumocytes was indicated by enhanced immunostaining of phospho-I[kappa]B[alpha] in these specific lung cell types. In vitro, the direct, particle-mediated effect on proinflammatory signalling in a rat lung epithelial (RLE) cell line was compared to the indirect, macrophage product-mediated effect. Treatment with quartz particles induced HO-1 and COX-2 mRNA expression in RLE cells in an NF-[kappa]B independent manner. Supernatant from quartz-treated macrophages rapidly activated the NF-[kappa]B signalling pathway in RLE cells and markedly induced iNOS mRNA expression up to 2000-fold compared to non-treated control cells. Neutralisation of TNF[alpha] and IL-1[beta] in macrophage supernatant did not reduce its ability to elicit NF-[kappa]B activation of RLE cells. In addition the effect was not modified by depletion or supplementation of intracellular glutathione.