In order to investigate whether products derived from the oxidation of sebum can be responsible for the induction of inflammatory processes, HaCaT keratinocytes were treated with peroxidated
squalene.
NF-kappaB activation, secretion, and expression of
IL-6, as well as
peroxisome proliferator-activated receptor alpha (
PPARalpha)
mRNA and
protein levels, were measured at the end of the treatment and after 24 and 48 hours of recovery.
Squalene peroxidation products were administered in amounts able to elicit significant hyperproliferation and to induce
lipoxygenase (LOX) activity. The results showed an early activation of
NF-kappaB followed by an increase in
PPARalpha mRNA and
protein levels. Moreover,
squalene peroxides induced an initial upregulation of
IL-6 production and secretion that was counteracted by
PPARalpha activation, as suggested by the subsequent decrease of
NF-kappaB nuclear translocation and
IL-6 levels. Inflammatory processes play an important role in the development of
acne vulgaris. In combination with our own previous findings, which indicated an association between LOX stimulation and increased percentage of proinflammatory
lipids in
acne as well as a correlation between increased
cytokine levels in the infundibulum, pilosebaceous duct hyperkeratinization, and augmented sebogenesis, the present data further support the involvement of
lipid peroxides, in particular
squalene peroxides, in establishing an inflammatory process in
acne.