title: Mycobacterium ulcerans mycolactone interferes with adhesion, migration and proliferation of primary human keratinocytes and HaCaT cell line.
abstract: The pathogenicity of Mycobacterium ulcerans (Buruli ulcer) is closely associated with the secretion of exotoxin mycolactone. The cytotoxicity of mycolactone has been linked to its apoptogenic activity. We explored if low mycolactone concentrations, which are not able to induce apoptosis, can influence other essential activities on two primary human keratinocyte populations, keratinocyte stem cells (KSC) and transit amplifying cells (TAC), and on a human keratinocyte line, HaCaT. We demonstrated that 0.01 and 0.1 ng/ml mycolactone A/B are not able to induce apoptosis in primary human keratinocytes, but interfere with KSC wound repair. Moreover, the same toxin concentrations reduce cell proliferation of KSC and TAC and their ability to adhere to type IV collagen. HaCaT cells are more resistant to the toxin; nevertheless, they show a delayed woud repair when treated with 1 and 10 ng/ml mycolactone A/B. Moreover, these sub-apoptotic concentrations affect their ability to proliferate and adhere to collagen IV. Wound healing is a complex mechanism, which occurs "in vivo" as the outcome of many co-ordinated events. Sub-apoptotic mycolactone concentrations can affect essential mechanisms, which are required to achieve wound repair, such as adhesion, migration and proliferation of human keratinocytes.
authors.affiliation: Department of Translational Medicine, University of Piemonte Orientale "A. Avogadro", Via Solaroli 17, 28100, Novara, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Graziola
authors.affiliation: Department of Translational Medicine, University of Piemonte Orientale "A. Avogadro", Via Solaroli 17, 28100, Novara, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Colombo
authors.affiliation: Dermatologic Department, "Maggiore della Carità" Hospital, Corso Mazzini 18, 28100, Novara, Italy.
authors.forename: Rossana
authors.initials: R
authors.lastname: Tiberio
authors.affiliation: Department of Translational Medicine, University of Piemonte Orientale "A. Avogadro", Via Solaroli 17, 28100, Novara, Italy.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Leigheb
authors.affiliation: Department of Translational Medicine, University of Piemonte Orientale "A. Avogadro", Via Solaroli 17, 28100, Novara, Italy. chiarella.bozzo@med.uniupo.it.
authors.forename: Chiarella
authors.initials: C
authors.lastname: Bozzo
mesh_terms: D000328:Adult; D017209:Apoptosis / Q000187:drug effects; D054312:Buruli Ulcer / Q000382:microbiology / Q000473:pathology; D002448:Cell Adhesion / Q000187:drug effects*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects*; D024141:Collagen Type IV / Q000378:metabolism; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism*; D018942:Macrolides / Q000378:metabolism / Q000494:pharmacology*; D008875:Middle Aged; D019911:Mycobacterium ulcerans / Q000472:pathogenicity*; D013234:Stem Cells / Q000187:drug effects / Q000378:metabolism; D014945:Wound Healing / Q000187:drug effects* / Q000502:physiology
chemical_list: D024141:Collagen Type IV; D018942:Macrolides; C117218:mycolactone; C451489:mycolactone B
keywords: Buruli ulcer; Keratinocytes; Mycolactone; Wound repair