The
monoterpene ascaridole, a fairly stable endoperoxide found in
essential oils such as
tea tree oil can provoke
allergic contact dermatitis which has been evidenced under patch test conditions. However, concomitantly we observed irritative skin reactions that demand further data underlining the sensitization potential of
ascaridole. Here, we studied the effects of
ascaridole on dendritic cell (DC) activation and
protein reactivity, 2 key steps of chemical-induced skin sensitization. Treatment of human monocyte-derived DC with
ascaridole found support for full DC maturation, a capability of sensitizers but not irritants. It induced significant upregulation of the expression of the costimulatory molecules CD86, CD80, CD40, and the adhesion molecule CD54 in a time-dependent manner. Maturation was accompanied by release of proinflammatory
cytokines interleukin (IL)-1ß,
tumor necrosis factor-α,
IL-6, and
IL-8. Similar to other chemical skin sensitizers including hydroperoxides, we observed a certain reactivity of
ascaridole toward
cysteine- but not
lysine-containing
peptides. During recent years, evidence accumulated for a radical mechanism as trigger for
protein reactivity of
peroxides. Treatment of the fairly stable endoperoxide
ascaridole with
iron as radical inducer ("activated
ascaridole") resulted in
cysteine peptide reactivity exceeding by far that of
ascaridole itself. Furthermore, activated
ascaridole showed increased potential for induction of the Nrf2 target gene
heme oxygenase 1 and upregulation of CD86 and CD54 on THP-1 cells, an established DC surrogate. These results indicate that radical formation could be involved in the steps leading to skin sensitization induced by the endoperoxide
ascaridole.