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Interleukin-6 counteracts effects of cyclosporin A on extracellular matrix metabolism by human dermal fibroblasts

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Abstract

Although the actions of cyclosporin (CyA) on keratinocyte are well established, little is known about its effects on dermal fibroblasts. Interleukin-6 (IL-6) is one of the inflammatory cytokines playing a pivotal role in certain skin diseases such as psoriasis. The aim of this study has been to determine whether CyA modifies the metabolism of extracellular matrix (ECM) by human fibroblasts in vitro. CyA altered the morphology of fibroblasts in the collagen matrix. Fibroblast proliferation was suppressed by CyA at 100 and 10 ng/ml. The production of type I collagen and tissue inhibitor of metalloproteinase 1 was also suppressed by CyA at 1000 ng/ml, and co-stimulation with IL-6 enhanced decreased production at 1000 and 100 ng/ml CyA. The production of matrix metalloproteinase 1 (MMP-1) was also suppressed by CyA in a dose-dependent manner. In contrast, the decreased production of MMP-1 was restored at 0.1–100 ng/ml CyA in the presence of IL-6. Regardless of the presence or absence of IL-6, the production of MMP-2 decreased at 1000 and 100 ng/ml, whereas the production of MMP-9 was unchanged. The production of transforming growth factor-β decreased at 100 ng/ml CyA. This study thus indicates that CyA influences ECM metabolism and the proliferation of human dermal fibroblasts, and that the effects of CyA are modulated by IL-6. CyA might also, in part, improve psoriatic skin by regulating the remodeling of ECM and by its action on immunocompetent cells.

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Authors and Affiliations

  1. Department of Dermatology, Gunma University Graduate School of Medicine, 3-39-22, Showa-machi, Maebashi, 371-8511, Japan

    Masatoshi Abe, Yoko Yokoyama, Tomoko Syuto, Hirohisa Ishibuchi & Osamu Ishikawa

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  1. Masatoshi Abe
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  2. Yoko Yokoyama
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  3. Tomoko Syuto
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  4. Hirohisa Ishibuchi
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  5. Osamu Ishikawa
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Correspondence to Masatoshi Abe.

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Abe, M., Yokoyama, Y., Syuto, T. et al. Interleukin-6 counteracts effects of cyclosporin A on extracellular matrix metabolism by human dermal fibroblasts. Cell Tissue Res 333, 281–288 (2008). https://doi.org/10.1007/s00441-008-0629-1

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  • DOI: https://doi.org/10.1007/s00441-008-0629-1

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