Basis for enhanced barrier function of pigmented skin

Mao Qiang Man, Tzu Kai Lin, Juan L. Santiago, Anna Celli, Lily Zhong, Zhi Ming Huang, Truus Roelandt, Melanie Hupe, John P. Sundberg, Kathleen A. Silva, Debra Crumrine, Gemma Martin-Ezquerra, Carles Trullas, Richard Sun, Joan S. Wakefield, Maria L. Wei, Kenneth R. Feingold, Theodora M. Mauro, Peter M. Elias*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

51 Scopus citations


Humans with darkly pigmented skin display superior permeability barrier function in comparison with humans with lightly pigmented skin. The reduced pH of the stratum corneum (SC) of darkly pigmented skin could account for enhanced function, because acidifying lightly pigmented human SC resets barrier function to darkly pigmented levels. In SKH1 (nonpigmented) versus SKH2/J (pigmented) hairless mice, we evaluated how a pigment-dependent reduction in pH could influence epidermal barrier function. Permeability barrier homeostasis is enhanced in SKH2/J versus SKH1 mice, correlating with a reduced pH in the lower SC that colocalizes with the extrusion of melanin granules. Darkly pigmented human epidermis also shows substantial melanin extrusion in the outer epidermis. Both acute barrier disruption and topical basic pH challenges accelerate reacidification of SKH2/J (but not SKH1) SC, while inducing melanin extrusion. SKH2/J mice also display enhanced expression of the SC acidifying enzyme, secretory phospholipase A2f (sPLA2f). Enhanced barrier function of SKH2/J mice could be attributed to enhanced activity of two acidic pH-dependent, ceramide-generating enzymes, β-glucocerebrosidase and acidic sphingomyelinase, leading to accelerated maturation of SC lamellar bilayers. Finally, organotypic cultures of darkly pigmented human keratinocytes display enhanced barrier function in comparison with lightly pigmented cultures. Together, these results suggest that the superior barrier function of pigmented epidermis can be largely attributed to the pH-lowering impact of melanin persistence/extrusion and enhanced sPLA2f expression.

Original languageEnglish
Pages (from-to)2399-2407
Number of pages9
JournalJournal of Investigative Dermatology
Issue number9
StatePublished - 09 2014
Externally publishedYes


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