An aPPARently protective mechanism for keratinocytes in wounded skin

Injury to the skin initiates an inflammatory response, which is mediated by an early infiltration of neutrophils, and subsequent recruitment of macrophages to the wound site. These cells release pro-inflammatory cytokines into the wound milieu, acting as a kick-start for downstream repair processes. Such signals influence various processes in the dermal compartment, but they are also responsible for keratinocyte activation. Recent work has identified peroxisome proliferator-activated receptor (PPAR) β/δ as a key mediator of epidermal effects. Induced via a stress-associated kinase cascade that targets an AP-1 site in its promoter region, PPARβ/δ was shown to stimulate keratinocyte migration and differentiation. Most interestingly, activation of this receptor protected keratinocytes from cytokine-induced apoptosis, suggesting that PPARβ/δ promotes survival of keratinocytes early after injury.