Cis-urocanic acid formation following far-UVC exposure and associated signaling responses in keratinocytes

Far-UVC (200-235 nm) has emerged as a safe and effective modality to inactivate pathogens in an indoor setting. trans-urocanic acid (UCA) is a chromophore that resides in the stratum corneum of the skin and is converted into the more biologically active cis isomer upon ultraviolet radiation (UVR) exposure where it initiates immunosuppression. The immunomodulatory potential of far-UVC exposure within the skin is currently unknown, particularly the conversion of trans- to cis-UCA and the resulting downstream signaling. Here, we confirm that far-UVC at 222 nm photoisomerizes trans-UCA into its cis isomer with levels comparable with solar simulated radiation (SSR). Further, we examined changes in cytokine secretion released from the supernatant and mRNA expression of IL-6 and IL-8 as well as key signaling mediators following far-UVC and SSR irradiation in primary human keratinocytes with or without irradiated UCA. Far-UVC alone induced modest non-significant trends in IL-6 and IL-8 secretion, ROS, and C-Jun phosphorylation. In the presence of irradiated UCA, higher mean levels of these mediators and increased STAT3 phosphorylation were observed 24 h post-exposure alongside elevated IL-6 and IL-8 expression. SSR-exposed keratinocytes also increased cytokine secretion; however, responses in the presence of irradiated UCA were associated with lower mean inflammatory signaling and increased p53 phosphorylation, accompanied by non-significant changes in NF-κB activity. Our findings demonstrate that far-UVC can induce trans-cis-UCA photoisomerization and highlight potential interactions between UCA and UVR-induced signaling pathways in keratinocytes. While biological variation in samples perhaps masks significant differences, these observations and trends can inform future work and contribute to a better understanding of chromophore-mediated photochemical processes that may influence cellular responses to far-UVC exposure.