Ultraviolet B radiation modifies circadian time in epidermal skin and in subcutaneous adipose tissue.

BACKGROUND: Recent findings suggest that circadian time regulates cellular functions in the skin and may affect protection against ultraviolet radiation (UVR). It is not known, however, whether UVR through skin directly affects the expression of circadian genes. We investigated the effect of ultraviolet B (UVB) exposure on cryptochrome circadian clock 1 (CRY1), cryptochrome circadian clock 2 (CRY2), and circadian associated repressor of transcription (CIART) genes. METHODS: Healthy volunteers (n = 12) were exposed to narrow-band UVB radiation of four standard erythemal dose (SED). Epidermal/dermal and subcutaneous adipose tissue samples were obtained by punch biopsies from irradiated and non-irradiated skin 10 cm away from the irradiated site 24 hours after UVB exposure. Gene expression of CRY1, CRY2, and CIART was measured using RT-PCR (TaqMan). RESULTS: Ultraviolet B radiation affected mRNA expression in the epidermal/dermal skin and in the subcutaneous adipose tissue. It down-regulated expression of CRY2 gene in the epidermal/dermal skin, whereas it up-regulated expression of CRY1 and CIART genes in the subcutaneous adipose tissue. CONCLUSION: We showed for the first time that UVB radiation affects expression of circadian genes in the subcutaneous adipose tissue. Further studies are warranted to understand the mechanisms in detail.

Narrow-band UVB radiation triggers diverse changes in the gene expression and induces the accumulation of M1 macrophages in human skin.

BACKGROUND: The underlying molecular mechanisms that determine the biological effects of UVB radiation exposure on human skin are still only partially comprehended. OBJECTIVES: Our goal is to examine the human skin transcriptome and related molecular mechanisms following a single exposure to UVB in the morning versus evening. METHODS: We exposed 20 volunteer females to four-fold standard erythema doses (SED4) of narrow-band UVB (309-313 nm) in the morning or evening and studied skin transcriptome 24 h after the exposure. We performed enrichment analyses of gene pathways, predicted changes in skin cell composition using cellular deconvolution, and correlated cell proportions with gene expression. RESULTS: In the skin transcriptome, UVB exposure yielded 1384 differentially expressed genes (DEGs) in the morning and 1295 DEGs in the evening, of which the most statistically significant DEGs enhanced proteasome and spliceosome pathways. Unexposed control samples showed difference by 321 DEGs in the morning vs evening, which was related to differences in genes associated with the circadian rhythm. After the UVB exposure, the fraction of proinflammatory M1 macrophages was significantly increased at both timepoints, and this increase was positively correlated with pathways on Myc targets and mTORC1 signaling. In the evening, the skin clinical erythema was more severe and had stronger positive correlation with the number of M1 macrophages than in the morning after UVB exposure. The fractions of myeloid and plasmacytoid dendritic cells and CD8 T cells were significantly decreased in the morning but not in the evening. CONCLUSIONS: NB-UVB-exposure causes changes in skin transcriptome, inhibiting cell division, and promoting proteasome activity and repair responses, both in the morning and in the evening. Inflammatory M1 macrophages may drive the UV-induced skin responses by exacerbating inflammation and erythema. These findings highlight how the same UVB exposure influences skin responses differently in morning versus evening and presents a possible explanation to the differences in gene expression in the skin after UVB irradiation at these two timepoints.

Melatonin immunoreactivity of epidermal skin is higher in the evening than morning but does not account for erythema sensitivity.

The skin is a site of melatonin synthesis, and melatonin has a role in protecting against ultraviolet radiation-induced damage. Ultraviolet B (UVB) induced erythema seems to vary between morning and evening. We investigated whether epidermal melatonin immunoreactivities in the morning differed from those in the evening, and whether UVB-induced erythema was associated with these melatonin immunoreactivities in healthy volunteers. Erythema sensitivity of the skin was determined in the morning and in the evening by scoring the Minimal Erythema Dose and quantifying the erythema index (EI). We took biopsies from the non-UVB-exposed skin of healthy volunteers (n = 39) in the morning and in the evening to study melatonin immunoreactivity with immunohistochemistry (IHC). In the IHC staining, there was more melatonin immunoreactivity in the evening than in the morning (p < .001). Erythema was more pronounced in the evening than in the morning irradiated skin (p < .001). The graded amount of melatonin immunoreactivity in the samples was not associated with the EI. We discovered melatonin immunoreactivity of the non-irradiated skin to vary diurnally. However, endogenous skin melatonin does not seem to be the reason why NB-UVB induces more erythema in the evening than in the morning.