The pigmentation phenotype of melanocytes affects their response to nitric oxide in vitro

It has been shown that nitric oxide (NO) can modulate the immune properties of epidermal melanocytes, and that overexpression of NO in the skin may contribute to inflammation-related pigmentary disorders. Little is known about whether constitutive cell pigmentation affects the sensitivity of melanocytes to NO. To compare the effect of NO on melanin synthesis and the expression of key melanogenesis-related genes in normal human melanocytes of various degrees of constitutive pigmentation. Human epidermal melanocytes derived from lightly and darkly pigmented skin (HEMn-LP and HEMn-DP, respectively) were cultured with or without a NO donor (SPER/NO). Then the total melanin content, the pheomelanin content, the activity and concentration of tyrosinase, and the expressions of and were assessed. NO released from SPER/NO did not alter the total amount of melanin produced by cultured cells but increased the proportion of pheomelanin, especially in HEMn-DP. Transcriptional activity of the melanogenesis-related genes, in particular , was downregulated in HEMn-DP and upregulated in HEMn-LP cultured with SPER/NO. NO can promote pheomelanogenesis in human epidermal melanocytes, and the cell response in this respect is associated with the pigmentation phenotype. During exposure to NO, melanocytes from dark skin produce much more pheomelanin than lightly pigmented cells. NO-induced overproduction of pheomelanin in the skin could be one of the factors responsible for the greater propensity to develop severe inflammatory dermatoses in dark-skinned individuals, or even melanoma formation based on local chronic inflammation.