Sulforaphane controls the release of paracrine factors by keratinocytes and thus mitigates particulate matter-induced premature skin aging by suppressing melanogenesis and maintaining collagen homeostasis

Background: Skin aging, potentially caused by exposure to particulate matter (PM)(2.)(5), is characterized by wrinkling, abnormal pigmentation, and skin dryness triggered by several keratinocyte-derived paracrine factors. Sulforaphane (4-methylsulfinylbutyl isothiocyanate, SFN), commonly found in cruciferous vegetables, has diverse biological effects on skin tissue. Purpose: In the present study, we have investigated whether SFN may alleviate PM2.5-induced premature skin aging. Methods: We used keratinocyte/melanocyte or keratinocyte/fibroblast coculture models of skin cells and measured the parameters of melanogenesis, collagen homeostasis and inflammation. Results: SFN inhibited the development of reactive oxygen species in keratinocytes exposed to PM2.5. In keratinocyte/melanocyte cocultures, it significantly inhibited the upregulation of melanogenic paracrine mediators (including endothelin-1 and prostaglandin E2) in keratinocytes exposed to PM2.5; the synthesis of melanogenic proteins including microphthalmia-associated transcription factor, tyrosinase-related protein 1, and tyrosinase; and the levels of melanin in melanocytes. SFN treatment of keratinocyte/fibroblast cocultures significantly reduced the PM 15 -induced expression of NF-kappa B-mediated cytokines including interleukin-1 beta, interleukin-6, tumor necrosis factor alpha, and cyclooxygenase-2. In fibroblasts of the keratinocyte/fibroblast coculture system, the expression levels of phospho-NF-kappa B, cysteine-rich protein 61, and matrix metalloproteinase-1 were significantly decreased whereas procollagen type I synthesis was significantly increased. Conclusion: Collectively, our results suggest that SFN mitigates PM2.5-induced premature skin aging by sup-pressing melanogenesis and maintaining collagen homeostasis. It acts by regulating the release of paracrine factors from keratinocytes.