antioxidants protect keratinocytes against m. ulcerans mycolactone cytotoxicity抗氧化剂保护角化细胞免受细菌内酯溃疡分枝杆菌细胞毒性.pdfVIP

Antioxidants Protect Keratinocytes against M. ulcerans Mycolactone Cytotoxicity ¨ 1 1 1 ˚ 1,2 2 Alvar Gronberg *, Louise Zettergren , Kerstin Bergh , Mona Stahle , Johan Heilborn , Kristian ¨ 3,4, Pamela L. Small5, Hannah Akuffo4, Sven Britton6 Angeby 1 Molecular Dermatology, Department of Medicine, Center for Molecular Medicine, Karolinska Institute, Stockholm, Sweden, 2 Department of Dermatology and Venereology, Karolinska University Hospital, Stockholm, Sweden, 3 Department of Clinical Microbiology, Karolinska University Hospital, Stockholm, Sweden, 4 Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, Stockholm, Sweden, 5 Department of Microbiology, University of Tennessee, Knoxville, Tennessee, United States of America, 6 Unit of Infectious Medicine, Karolinska University Hospital, Stockholm, Sweden Abstract Background: Mycobacterium ulcerans is the causative agent of necrotizing skin ulcerations in distinctive geographical areas. M. ulcerans produces a macrolide toxin, mycolactone, which has been identified as an important virulence factor in ulcer formation. Mycolactone is cytotoxic to fibroblasts and adipocytes in vitro and has modulating activity on immune cell functions. The effect of mycolactone on keratinocytes has not been reported previously and the mechanism of mycolactone toxicity is presently unknown. Many other macrolide substances have cytotoxic and immunosuppressive activities and mediate some of their effects via production of reactive oxygen species (ROS). We have studied the effect of mycolactone in vitro