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

Phytomedicine. 2020 Oct:77:153276. doi: 10.1016/j.phymed.2020.153276. Epub 2020 Jul 1.

Abstract

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 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.

Conclusion: 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.

Keywords: Coculture system; Collagen homeostasis; Melanogenesis; Particulate matter 2.5; Premature skin aging; Sulforaphane.

MeSH terms

  • Coculture Techniques
  • Collagen / metabolism*
  • Cytokines / metabolism
  • Fibroblasts / drug effects
  • Homeostasis / drug effects
  • Humans
  • Isothiocyanates / pharmacology*
  • Keratinocytes / drug effects*
  • Keratinocytes / metabolism
  • Melanins / biosynthesis
  • Melanocytes / drug effects
  • Melanocytes / metabolism
  • Paracrine Communication / drug effects
  • Particulate Matter / adverse effects*
  • Reactive Oxygen Species / metabolism
  • Skin Aging / drug effects*
  • Sulfoxides

Substances

  • Cytokines
  • Isothiocyanates
  • Melanins
  • Particulate Matter
  • Reactive Oxygen Species
  • Sulfoxides
  • Collagen
  • sulforaphane