UPTAKE OF SILICA AND CARBON NANOTUBES BY HUMAN MACROPHAGES/MONOCYTES INDUCES ACTIVATION OF FIBROBLASTS IN VITRO - POTENTIAL IMPLICATION FOR PATHOGENESIS OF INFLAMMATION AND FIBROTIC DISEASES

The potential pathogenic effects of silica and carbon nanotubes (CNTs) on fibroblasts, macrophages/monocytes, and T cells were investigated. Human macrophage/monocytes were cultured and stimulated with silica, CNTs, or titanium particles. After adding human T cells to the stimulated macrophages/monocytes, the cells were added to cultured human fibroblasts. Upon microscopic examination, CNT stimulation after 24 hours showed centralization of macrophages/monocytes around the CNTs. Silica stimulation showed a significant increase of IL-1 alpha and IL-1 beta in cultured medium, and an increased gene expression of CTGF in cultured fibroblasts at 1 hour, as well as an up-regulation of the COL1A2 gene at 24-hour time point. In addition to the same changes of IL-1 alpha, I L-1 beta and the COL1A2 by silica, CNT stimulation showed an increase of IL-8 in cultured medium at 1-hour time point. Titanium stimulation yielded no significant changes. The results indicate a proinflammatory and/or profibrotic effect of silica and CNTs to cultured human cells including macrophages/monocyte, T cells and fibroblasts.