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-1α and IL-1β 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-1α, IL-1β 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.
University of Texas Medical School at Houston, Internal Medicine, Houston, TX 77030, USA.
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D002450:Cell Communication / Q000187:drug effects*; D045744:Cell Line, Tumor; D048430:Cell Shape / Q000187:drug effects; D018920:Coculture Techniques; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism; D055513:Connective Tissue Growth Factor / Q000235:genetics / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D005355:Fibrosis; D006801:Humans; D007249:Inflammation / Q000139:chemically induced* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D018836:Inflammation Mediators / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D037742:Nanotubes, Carbon / Q000633:toxicity*; D012822:Silicon Dioxide / Q000378:metabolism / Q000633:toxicity*; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D013997:Time Factors; D014025:Titanium / Q000633:toxicity; D015854:Up-Regulation
C526317:CCN2 protein, human; D024042:Collagen Type I; D016207:Cytokines; D018836:Inflammation Mediators; D037742:Nanotubes, Carbon; D055513:Connective Tissue Growth Factor; D012822:Silicon Dioxide; D014025:Titanium