RNASE2 and freckles: As for the biological mechanisms leading to the increased activities of the EDN and SCF signaling cascades, our in vitro studies suggested that while the upregulation of IL-1α is mainly responsible for stimulating EDN1 and SCF production in UVB-melanosis, the upregulation of TNFα is associated with the stimulated production of those same two cytokines in SLs.