Basis for Enhanced Barrier Function of Pigmented Skin

Abstract

Humans with darkly-pigmented skin display superior permeability barrier function in comparison to 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 (non-pigmented) vs. 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 vs. SKH1 mice, correlating with a reduced pH in the lower SC that co-localizes 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 re-acidification 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-bearing human keratinocytes display enhanced barrier function in comparison to 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.

Topical Histamine Stimulates Repigmentation of Nonsegmental Vitiligo by a Receptor-Dependent Mechanism

“…In contrast, topical histamine-induced pigmentation is accompanied by an acceleration of permeability barrier recovery, consistent with our prior findings that pigmentation benefits permeability barrier homeostasis [36,37]. While the mechanisms by which topical histamine improves the permeability barrier in vitiligo are unknown, Gutowska-Owsiak et al [42] reported that histamine upregulates the expression of cornified envelope proteins, such as small proline-rich proteins and protease inhibitors.…”

“…Our previous studies demonstrated that epidermal pigmentation benefits the epidermal permeability barrier [36,37]. To determine whether the topical histamine-induced improvement in pigmentation is paralleled by an enhancement of permeability barrier homeostasis, both basal transepidermal water loss and barrier recovery kinetics were assessed following 5 weeks of treatment of vitiligo lesions with topical histamine.…”

A new era of secreted phospholipase A2

“…sPLA 2 -IIF is abundantly expressed in the suprabasal epidermis ( 79,80 ). Gene disruption of sPLA 2 -IIF ( Pla2g2f Ϫ / Ϫ ) has been reported to impair the acidifi cation of the stratum corneum and delay recovery of the skin barrier after tape-stripping ( 79 ), although a mechanistic insight is currently obscure and it should be confi rmed or expanded in other ongoing studies.…”

Evolution of Skin Color

“…The answer almost certainly relates to the most critical function of the skin-the provision of a competent permeability barrier, which is a requirement for life in a desiccating terrestrial environment (previously proposed in ). Finally, the skin of pigmented hairless mice (Skh2) displays a superior permeability barrier in comparison with the nonpigmented skin of albino (Skh1) hairless mice (Man et al, 2014). Moreover, patients with vitiligo, whose pigment loss occurs in localized patches due to an absence of melanocytes, display reduced barrier function in depigmented regions (Liu et al, 2010).…”

“…Darkly pigmented human skin possesses a more competent skin barrier than does more lightly pigmented skin, a difference that correlates solely with pigment type rather than ethnicity, and is independent of latitude of residence (Reed et al, 1995;Gunathilake et al, 2009). Mechanistic studies show that the reduced pH of darkly pigmented skin largely but not completely accounts for these differences, because exogenous acidification of the stratum corneum "resets" barrier function to levels seen in darkly pigmented subjects Man et al, 2014). Finally, the skin of pigmented hairless mice (Skh2) displays a superior permeability barrier in comparison with the nonpigmented skin of albino (Skh1) hairless mice (Man et al, 2014).…”