Surface Lipids as Multifunctional Mediators of Skin Responses to Environmental Stimuli

Abstract

Skin surface lipid (SSL) film is a mixture of sebum and keratinocyte membrane lipids, protecting skin from environment. Its composition is unique for the high percentage of long chain fatty acids, and of the polyterpenoid squalene, absent in other human tissues, and in non-human Primates sebum. Here, the still incomplete body of information on SSL as mediators of external chemical, physical, and microbial signals and stressors is revised, focusing on the central event of the continuous oxidative modification induced by the metabolic activity of residential and pathological microbial flora, natural or iatrogenic UV irradiation, exposure to chemicals and cosmetics. Once alpha-tocopherol and ubiquinol-10 antioxidant defences of SSL are overcome, oxidation of squalene and cholesterol gives rise to reactive by-products penetrating deeper into skin layers, to mediate local defensive inflammatory, photo-protective, immune reactions or, at higher concentrations, inducing local but also systemic immune depression, ultimately implicating skin cancerogenesis. Qualitative modifications of SSL represent a pathogenetic sign of diagnostic value in dermatological disorders involving altered sebum production, like pytiriasis versicolor, acne, atopic or seborrheic dermatitis, as well as photo-aging. Achievements of nutriceutical interventions aimed at restoring normal SSL composition and homeostasis are discussed, as feasible therapeutic goals and major means of photo-protection.

Beyond acne: Current aspects of sebaceous gland biology and function

“…The skin surface lipid (SSL) film, a mixture of sebum and keratinocyte membrane lipids, is the first barrier against environmental stress [134]. Among the ingredients of SSL, squalene, a key biosynthetic precursor of cholesterol secreted by SGs, and α-tocopherol (vitamin E) secreted together with lipids from sebaceous gland, provide collaboratively antioxidant protection to the skin surface [135][136][137].…”

Secondary Plant Metabolites for Sun Protective Cosmetics: From Pre-Selection to Product Formulation

“…The outmost external photo-chemical barrier encountered by environmental radiations is the skin surface lipids, a protective hydrophobic film occurring more abundantly in the most photo-exposed cutaneous districts [1]. The lipid barrier is a mixture of epidermal lipids, deriving: (a) from the exfoliating stratum corneum, mainly composed of keratinocyte debris phospholipids and their products of hydrolysis, and (b) from lipids, triglycerides, sterols, and lipophilic vitamins (vitamin E and coenzyme Q 10 ) produced by sebaceous glands.…”

“…Although squalene has long been considered a double edge sword: if produced by sebaceous glands or applied to the skin in excessive amounts, squalene could give an uncontrolled rise of toxic aldehydes and epoxides, which are not sufficiently metabolised by the built in skin antioxidant systems. In this case, squalene may be responsible for the pro-inflammatory, pro-ageing, and tumour-promoting cutaneous photo-oxidative damage (reviewed in [1]). The rate of squalene degradation has been therefore proposed as a feasible parameter to measure the efficacy of sun-protecting formulations [33].…”

“…Then, UV photo-chemically modifies non-viable keratinocytes and intercellular lipids of the stratum corneum. Finally, it reaches directly or by means of photo-chemical mediators the viable layers of epidermis and the underlying dermal compartments [1]. Upon exposure to UV radiation or to photo-chemical mediators, skin keratinocytes mount characteristic inflammatory, metabolic, and proliferative responses in an attempt for self-protection from and adaptation to UV-induced damage [2].…”

Oxidization of squalene, a human skin lipid: a new and reliable marker of environmental pollution studies

“…In a comparable approach, topical applications of squalene peroxides onto the skin of guinea-pigs led to a hyperpigmentation through a release of prostaglandin E 2 by keratinocytes [36]. In humans, oxidized surface lipids are viewed as potent inflammatory mediators in some skin afflictions such as pityriasis versicolour or seborrhoeic dermatitis [37].…”