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Abstract: In order to evaluate the degree of pulmonary fibrosis and to identify the fibrogenic mechanisms induced by ultrafine amorphous silica (UFAS), UFAS suspensions (∼50μl) were instilled intratracheally into A/J mice at doses of 0, 2, 10 and 50mg/kg (n =5 per group). Mice were sacrificed at 24h, 1, 4 and 14weeks after exposure. Gomori’s trichrome staining revealed that UFAS induced severe alveolar epithelial thickening and pulmonary fibrosis at 1week, though animals almost recovered at 4 and 14weeks. The mRNA and protein levels of cytokines (IL-4, IL-10, IL-13 and IFN-γ), matrix metalloproteinases (MMP-2, MMP-9 and MMP-10) and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) in lung tissues were significantly elevated at 24h and 1week post-treatment, though these levels decreased to near the control range at 4 and 14weeks except IFN-γ and MMP-2. These results demonstrate that UFAS can induce pulmonary fibrosis in the same way as crystalline silica. However, the degree of fibrosis observed was transient. This study shows that cytokines (IL-4, IL-10, IL-13 and IFN-γ), MMPs (MMP-2, MMP-9 and MMP-10) and TIMP-1 play important roles in the fibrosis induced by the intratracheal instillation of UFAS. [Copyright &y& Elsevier]

Abstract: In order to evaluate the pulmonary effects and inflammatory mechanisms of ultrafine amorphous silica particles (UFASs), the UFASs suspension was prepared in PBS and intratracheally administered to A/J mice at doses of 0, 2, 10 and 50mg/kg (n =5 per group). Animals were sacrificed at 24h, and 1, 4 or 14 weeks following exposures. At each time point, a bronchoalveolar lavage fluid analysis, histopathological examination, quantitative real-time PCR and immunohistochemistry of the lung tissues were assessed. The intratracheal instillation of UFASs significantly increased the lung weights and total BAL cells following exposures. The histopathological examination revealed that UFASs-induced severe inflammation, with neutrophils, at an early stage and chronic granulomatous inflammation at the later stage. The mRNA and protein levels of IL-1β, IL-6, IL-8, TNF-α, MCP-1 and MIP-2 in lung tissues were significantly increased during the early stages, but there were no changes after weeks 1 (TNF-α) or 4 (IL-1β, IL-6, IL-8, MCP-1 and MIP-2). Instillation of UFASs-induced transient, but very severe lung inflammation. Therefore, the cytokines (IL-1β, IL-6, IL-8 and TNF-α) and chemokines (MCP-1 and MIP-2) play important roles in the inflammation induced by the intratracheal instillation of UFASs. [Copyright &y& Elsevier]