Targets, Volume 2, Issue 4 (December 2024) – 1 article

Glucocorticoids are the mainstay treatments for diverse pathologies. Ultraviolet (UV) radiation is a risk factor for alterations in the skin, including cell viability (skin thickness), mediators of angiogenesis (blood flow/inflammation), and remodeling of the extracellular matrix (skin integrity). We examined the effects of hydrocortisone on cell viability, p53 promoter activity, and expression of interleukin-8 (IL-8), matrixmetalloproteinase-1 (MMP-1), and tissue inhibitor of matrixmetalloproteinase-1 (TIMP-1) in non-irradiated, UVA-radiated, and UVB-irradiated dermal fibroblasts and melanoma cells. Hydrocortisone inhibited cell viability by stimulating p53 promoter activity in fibroblasts, but not in melanoma cells, which instead showed a decrease in p53 promoter activity in non-irradiated and UVA-irradiated cells. Hydrocortisone inhibited the IL-8 protein levels in non-irradiated and UV-irradiated fibroblasts, and in the non-irradiated melanoma cells, by post-transcriptional mechanisms. Hydrocortisone increased the MMP-1 to TIMP-1 ratio in non-irradiated and UVB-irradiated fibroblasts by inhibiting TIMP-1, and in melanoma cells by inhibiting TIMP-1 in non-irradiated cells and stimulating MMP-1 in UV-irradiated cells. It may be inferred that hydrocortisone has the potential to cause skin thinning by inhibiting cell viability, angiogenesis, and deposition of structural ECM by fibroblasts, regardless of UV exposure, and facilitating UV-exposed melanoma cells by increasing MMP-1 expression. Full article