A Mycobacterium ulcerans toxin,mycolactone, induces apoptosis in primary human keratinocytes and in HaCaT cells |
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Authors: | Chiarella Bozzo Rossana Tiberio Francesca Graziola Ginevra Pertusi Guido Valente Enrico Colombo Pamela LC Small Giorgio Leigheb |
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Institution: | 1. Noguchi Memorial Institute for Medical Research, University of Ghana, P. O. Box LG 581, Accra, Ghana;2. Antimicrobial Agents Unit, Laboratory for Phytobiochemistry and Medicinal Plants Study, Faculty of Science, University of Yaoundé 1, P.O. 812 Yaoundé, Cameroon |
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Abstract: | The pathogenicity of Mycobacterium ulcerans (Buruli ulcer) depends on cytotoxic effect of its exotoxin mycolactone. Since epidermis represents a barrier against infectious agents and balanced apoptosis is essential in epidermal homeostasis, we explored if mycolactone A/B induces apoptosis on two human keratinocyte populations, stem cells (KSC) and transit amplifying cells (TAC), and on human keratinocyte line, HaCaT. Treatment of TAC with 1 and 10 ng/ml mycolactone-induced 60 and 90% apoptosis. KSC were more resistant than TAC: 50 and 75% of cells underwent apoptosis after 10 and 100 ng/ml toxin-treatment. Higher doses (1000 ng/ml) induced about 30% apoptosis on HaCaT. In contrast, mycolactone A/B was devoid of toxicity neither on human hepatoma HuH7 nor on human embryonic kidney HEK 293 T cell lines. In conclusion, mycolactone induces apoptosis in human keratinocytes, thus contributing to Buruli ulcer lesions development. |
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