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Effects of commonly used immunosuppressants on graft-derived fibroblasts
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences. (Transplantationskirurgi)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences. plastikkirurgi. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Plastic Surgery.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences. (Transplantationskirurgi)
2004 (English)In: Clinical and Experimental Immunology, ISSN 0009-9104, Vol. 136, no 3, 405-412 p.Article in journal (Refereed) Published
Abstract [en]

In acute rejection of transplanted organs intragraft fibroblasts increase their production of hyaluronan. Hyaluronan has strong water binding capacity and an increased tissue content of hyaluronan thus contributes to the development of interstitial oedema. The present study examined the effects of commonly used immunosuppressants (prednisolone, cyclosporin, tacrolimus, mycophenolic acid and sirolimus) on fibroblast proliferation, hyaluronan production and cell surface receptor expression. Fibroblasts isolated from rejecting tissue and from normal, non-transplanted tissue were studied in parallel. All substances investigated, except tacrolimus, were found to affect fibroblasts in one way or another. The most striking effect was the almost total inhibition of fibroblast proliferation in the presence of mycophenolic acid. Cyclosporin reduced the proliferation by about 50% and prednisolone had an inhibiting effect on hyaluronan production (50% reduction). These effects were observed on fibroblasts isolated from rat cardiac allografts undergoing rejection as well as on fibroblasts obtained from normal heart tissue. In contrast, sirolimus was found to stimulate the proliferation of fibroblasts from rejecting tissue (100% increase), but not that of normal fibroblasts. The majority of the fibroblasts expressed the hyaluronan receptor CD44, with a more intense expression in cultures of fibroblasts derived at rejection. None of the immunosuppressants affected the staining pattern (number of positive cells or intensity). The inhibitory effects of prednisolone, cyclosporin and mycophenolic acid on fibroblasts may contribute to the overall beneficial effects of these drugs when used for prevention or treatment of rejection.

Place, publisher, year, edition, pages
2004. Vol. 136, no 3, 405-412 p.
Keyword [en]
fibroblasts, hyaluronan, immunosuppression, proliferation
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-72706DOI: 10.1111/j.1365-2249.2004.02488.xPubMedID: 15147341 OAI: oai:DiVA.org:uu-72706DiVA: diva2:100617
Available from: 2006-12-20 Created: 2006-12-20 Last updated: 2009-05-07Bibliographically approved

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Johnsson, CeciliaGerdin, BengtTufveson, Gunnar

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