title: A Mycobacterium ulcerans toxin, mycolactone, induces apoptosis in primary human keratinocytes and in HaCaT cells.
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.
authors.affiliation: Department of Clinical and Experimental Medicine, University of Piemonte Orientale A. Avogadro, Via Solaroli 17, 28100 Novara, Italy. bozzo@med.unipmn.it
authors.forename: Chiarella
authors.initials: C
authors.lastname: Bozzo
authors.forename: Rossana
authors.initials: R
authors.lastname: Tiberio
authors.forename: Francesca
authors.initials: F
authors.lastname: Graziola
authors.forename: Ginevra
authors.initials: G
authors.lastname: Pertusi
authors.forename: Guido
authors.initials: G
authors.lastname: Valente
authors.forename: Enrico
authors.initials: E
authors.lastname: Colombo
authors.forename: Pamela L C
authors.initials: PL
authors.lastname: Small
authors.forename: Giorgio
authors.initials: G
authors.lastname: Leigheb
mesh_terms: D000328:Adult; D017209:Apoptosis; D002478:Cells, Cultured; D022781:Hepatocytes / Q000187:drug effects; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects*; D007783:Lactones / Q000378:metabolism / Q000633:toxicity*; D018942:Macrolides; D008875:Middle Aged; D019911:Mycobacterium ulcerans / Q000378:metabolism / Q000472:pathogenicity*
chemical_list: D007783:Lactones; D018942:Macrolides; C451488:mycolactone A; C451489:mycolactone B