Abstract
The study aimed to identify endogenous lipid mediators of metabolic and inflammatory responses of human keratinocytes to solar UV irradiation. Physiologically relevant doses of solar simulated UVA+UVB were applied to human skin surface lipids (SSL) or to primary cultures of normal human epidermal keratinocytes (NHEK). The decay of photo-sensitive lipid-soluble components, alpha-tocopherol, squalene (Sq), and cholesterol in SSL was analysed and products of squalene photo-oxidation (SqPx) were quantitatively isolated from irradiated SSL. When administered directly to NHEK, low-dose solar UVA+UVB induced time-dependent inflammatory and metabolic responses. To mimic UVA+UVB action, NHEK were exposed to intact or photo-oxidised SSL, Sq or SqPx, 4-hydroxy-2-nonenal (4-HNE), and the product of tryptophan photo-oxidation 6-formylindolo[3,2-b]carbazole (FICZ). FICZ activated exclusively metabolic responses characteristic for UV, i.e. the aryl hydrocarbon receptor (AhR) machinery and downstream CYP1A1/CYP1B1 gene expression, while 4-HNE slightly stimulated inflammatory UV markers IL-6, COX-2, and iNOS genes. On contrast, SqPx induced the majority of metabolic and inflammatory responses characteristic for UVA+UVB, acting via AhR, EGFR, and G-protein-coupled arachidonic acid receptor (G2A).Conclusions/SignificanceOur findings indicate that Sq could be a primary sensor of solar UV irradiation in human SSL, and products of its photo-oxidation mediate/induce metabolic and inflammatory responses of keratinocytes to UVA+UVB, which could be relevant for skin inflammation in the sun-exposed oily skin.
Highlights
Numerous mechanisms have been evolved in human skin to sense environmental stimuli and to mount adaptive responses in order to maintain homeostasis in the skin and protect the entire organism
Conclusions/Significance: Our findings indicate that Sq could be a primary sensor of solar UV irradiation in human skin surface lipids (SSL), and products of its photo-oxidation mediate/induce metabolic and inflammatory responses of keratinocytes to UVA+UVB, which could be relevant for skin inflammation in the sun-exposed oily skin
We showed for the first time that photo-oxidised squalene photooxidation (SqPx) directly applied to primary human epidermal keratinocytes (NHEK) mimics the majority of UVA+UVB effects towards primary human epidermal keratinocytes (NHEK), by stimulating the aryl hydrocarbon receptor (AhR)-controlled metabolic pathway and affecting epidermal growth factor receptor (EGFR)- and G2A-connected inflammatory responses
Summary
Numerous mechanisms have been evolved in human skin to sense environmental stimuli and to mount adaptive responses in order to maintain homeostasis in the skin and protect the entire organism. Both are continuously produced by skin surface-open sebaceous glands to maintain their physiologically essential levels and substitute photo-destructed molecules [1,2,3]. The role of Sq and its oxidation products (SqPx) in skin photo-protection [9] and in the induction of inflammatory responses of keratinocytes in the context of acne pathogenesis [10] has been evaluated and recently reviewed in [2], [3]
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