The oxidant stress can alter the function of protein through the reversible oxidation of the thiolic group of sensitive cysteine residues. In particular, these terpenes induce S-glutathionylation of STAT3 hindering its tyrosine phosphorylation and activation. In this study, we showed that treatments of human keratinocytes with DCE and CS Ciclesonide resulted in a substantial reduction of intracellular GSH levels and inhibition of STAT3 phosphorylation and activation. DCE and CS also inhibit STAT1 phosphorylation whereas significantly enhance EGFR and ERK1/2 cascades. These DCE or CS-induced effects in keratinocytes are particularly important, since few Amiodarone molecules have been found so far to inhibit STAT3 and STAT1-dependent inflammatory pathways and, in parallel, to activate the anti-inflammatory EGFR and ERK1/2 molecules in keratinocytes. Other molecules influencing GSH levels, such as 1-buthionine sulphoximine, a glutamylcysteine synthase inhibitor, have been found to regulate STAT3 and ERK1/2 activation, even though they decrease synthesis of GSH rather than sequestering and oxidizing it. However, differently from DCE and CS, these molecules can have opposite effects depending on cell type and stimuli inducing STAT3 or ERK1/2. For instance, BSO inhibits STAT3 or ERK1/2 induced by leukemia inhibitory factor in cardiac myocytes, whereas it has no effects on IL-6-induced STAT3 activation in endothelial cells. On the other end, BSO can promote STAT3 activation in rat fibroblasts and epidermally derived A431 cells, as well as in rat livers. A number of previous studies showed that DCE and CS inhibit proliferation and enhance apoptosis in different human cancer cells. Specifically they can promote mitotic arrest accompanied by modulation of proteins involved in cell-cycle progression, including Chk2, Cdc25c, Cdk1, cyclin B1. We found that DCE or CS treatments efficiently induced apoptosis as well as inhibited proliferation in cultured human keratinocytes, either in basal conditions or in presence of IL-22.Proliferation inhibition was not due to cytotoxic effects of terpenes lactones but it was associated instead to cell-cycle arrest of keratinocytes in G2/ M phases, and concomitant decreased expression of cyclin D1, PCNA and p-RB proteins.