Keratinocyte-derived paracrine factors regulate stress response of melanocytes to UVB

Abstract

The skin microenvironment created by keratinocytes (KC) influences stress responses of melanocytes (MC) to UVB insult. Here, we investigated paracrine factors involved in the regulatory role of microenvironment created by KC in UVB-mediated MC responses using RNA sequencing analysis as well as in vitro and in vivo models. RNA-Seq showed that G-CSF and CCL20 genes were highly upregulated in UVB-irradiated KC and their levels best correlated with paracrine protective effects of KC on stress responses of MC to UVB. Recombinant G-CSF and CCL20 treatment revealed the strongest modulatory effects on UVB-induced MC responses by mitigating apoptosis and ROS formation and upregulating tyrosinase and tyrosinase-related protein-1 (TRP-1) involved in the melanogenic pathway. A similar correlation between G-CSF and CCL20 expression in KC and the tyrosinase level in MC was also observed in the UVB-irradiated mouse skin. Our study reports for the first time that G-CSF and CCL20 might play a regulatory role in the KCs paracrine effects on UVB-mediated MC damage and also provides translational insights for the development of biomarkers for predicting susceptibility to photodamage. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=185 SRC="FIGDIR/small/523939v1_ufig1.gif" ALT="Figure 1"> View larger version (58K): org.highwire.dtl.DTLVardef@113588org.highwire.dtl.DTLVardef@1d1af40org.highwire.dtl.DTLVardef@1489df0org.highwire.dtl.DTLVardef@7935c5_HPS_FORMAT_FIGEXP M_FIG C_FIG