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

•PM2.5 induces premature skin aging in keratinocyte-melanocyte and keratinocyte/fibroblast coculture systems.•SFN suppresses increases reactive oxygen species and levels of melanogenic paracrine mediators and cytokines in PM2.5-stimulated keratinocytes.•SFN mitigates PM2.5-induced skin aging by suppressing melanogenesis and maintaining collagen homeostasis. 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. In the present study, we have investigated whether SFN may alleviate PM2.5-induced premature skin aging. We used keratinocyte/melanocyte or keratinocyte/fibroblast coculture models of skin cells and measured the parameters of melanogenesis, collagen homeostasis and inflammation. 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 PM2.5-induced expression of NF-κB-mediated cytokines including interleukin-1β, interleukin-6, tumor necrosis factor α, and cyclooxygenase-2. In fibroblasts of the keratinocyte/fibroblast coculture system, the expression levels of phospho-NF-κB, cysteine-rich protein 61, and matrix metalloproteinase-1 were significantly decreased whereas procollagen type I synthesis was significantly increased. Collectively, our results suggest that SFN mitigates PM2.5-induced premature skin aging by suppressing melanogenesis and maintaining collagen homeostasis. It acts by regulating the release of paracrine factors from keratinocytes. Schematic illustration of the anti-premature skin aging effects of SFN in keratinocyte/melanocyte or keratinocyte/fibroblast coculture systems. After PM2.5 exposure, keratinocytes produced high levels of ROS, paracrine mediators, and inflammatory cytokines. In the keratinocyte/melanocyte coculture system, SFN inhibited hyperp