TY - JOUR
T1 - A Mycobacterium ulcerans toxin, mycolactone, induces apoptosis in primary human keratinocytes and in HaCaT cells
AU - Bozzo, Chiarella
AU - Tiberio, Rossana
AU - Graziola, Francesca
AU - Pertusi, Ginevra
AU - Valente, Guido
AU - Colombo, Enrico
AU - Small, Pamela L.C.
AU - Leigheb, Giorgio
PY - 2010/12
Y1 - 2010/12
N2 - 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.
AB - 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.
KW - Apoptosis
KW - Buruli ulcer
KW - Keratinocyte stem cells
KW - Mycolactone
KW - Primary human keratinocytes
KW - Transit amplifying cells
UR - https://www.scopus.com/pages/publications/78149488817
U2 - 10.1016/j.micinf.2010.08.005
DO - 10.1016/j.micinf.2010.08.005
M3 - Article
SN - 1286-4579
VL - 12
SP - 1258
EP - 1263
JO - Microbes and Infection
JF - Microbes and Infection
IS - 14-15
ER -
