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            ‐Acyl ethanolamide and eicosanoid involvement in irritant dermatitis

Kendall, Alexandra C.; Pilkington, Suzanne M.; Sassano, Gary; Rhodes, Lesley E.; Nicolaou, Anna

doi:10.1111/bjd.14521

Cited by 27 publications

(29 citation statements)

References 68 publications

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“…We propose that the UVR reduction in cutaneous PGD 2 could partially reflect loss of LC from the epidermis. This is supported by our observation of no UVR‐induced PGD 2 reduction in human primary keratinocytes and fibroblasts (A. Nicolaou), or in the dermal fraction of human skin . In mice, ageing‐associated increases in local PGD 2 correlate with impaired migration of respiratory DC, and antagonism of the DP1 receptor restores migration .…”

Section: Discussionsupporting

confidence: 65%

Effect of oral eicosapentaenoic acid on epidermal Langerhans cell numbers and PGD₂ production in UVR‐exposed human skin: a randomised controlled study

Pilkington

Gibbs

Costello

et al. 2016

Experimental Dermatology

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28Langerhans cells (LC) are sentinels of skin's immune system, their loss from epidermis 29 contributing to UVR-suppression of cell mediated immunity (CMI). Omega-3 polyunsaturated 30 fatty acids can show potential to abrogate UVR-suppression of CMI in mice and humans, 31 potentially through modulation of LC migration. Our objectives were to examine if 32 eicosapentaenoic acid (EPA) ingestion influences UV-mediated effects on epidermal LC 33 numbers and levels of immunomodulatory mediators including prostaglandin (PG)D 2 , which 34 is expressed by LC. 35In a double-blind randomised controlled study, healthy individuals took 5g EPA-rich 36 (n=40) or control (n=33) lipid for 12-weeks; UVR exposed and unexposed skin samples were 37 taken pre-and post-supplementation. Epidermal LC numbers were assessed by 38 immunofluorescence for CD1a, and skin blister fluid PG and cytokines quantified by LC-39 MS/MS and Luminex assay, respectively. Pre-supplementation, UVR reduced mean (SEM) 40LC number/mm 2 from 913 (28) to 322 (40) (p<0.001), and mean PGD 2 level by 37% from 8.1 41 (11.6) to 5.1 (5.6) pg/µl; p<0.001), while IL-8 level increased (p<0.001). Despite confirmation 42 of EPA bioavailability in red blood cells and skin in the active group, no between-group effect 43 of EPA was found on UVR-modulation of LC numbers, PGD 2 or cytokine levels post-44 supplementation. 45

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Section: Discussionsupporting

confidence: 65%

Effect of oral eicosapentaenoic acid on epidermal Langerhans cell numbers and PGD₂ production in UVR‐exposed human skin: a randomised controlled study

Pilkington

Gibbs

Costello

et al. 2016

Experimental Dermatology

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“…Skin (1 punch biopsy per time point, 120–250 mg) was divided into dermis and epidermis by scalpel at × 40 magnification, and lipids were extracted as previously described [16], [17]. Although a scalpel does not produce a completely clean separation of the dermis and epidermis, and some dermal contamination of the epidermis remains, this method prevents any degradation of the lipids that occurs during other separation techniques that depend on incubation in salts, enzymes or extreme temperatures [56], [57], and care was taken not to allow any epidermal contamination of the dermis.…”

Section: Methodsmentioning

confidence: 99%

“…As well as contributing to the structural integrity of the skin, PUFA such as LA, AA, eicosapentaenoic acid (EPA; C20:5n-3) and docosahexaenoic acid (DHA; C22:6n-3) are metabolized to octadecanoids, eicosanoids, docosanoids, endocannabinoids and related bioactive lipid species, known to mediate inflammatory and immune reactions in many tissues, including skin [13], [14], [15], [16], [17].…”

Section: Introductionmentioning

confidence: 99%

Lipid functions in skin: Differential effects of n-3 polyunsaturated fatty acids on cutaneous ceramides, in a human skin organ culture model

Kendall

Kiezel-Tsugunova

Brownbridge

et al. 2017

Biochimica et Biophysica Acta (BBA) - Biomembranes

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Ceramides are important for skin health, with a multitude of species found in both dermis and epidermis. The epidermis contains linoleic acid-Ester-linked Omega-hydroxylated ceramides of 6-Hydroxy-sphingosine, Sphingosine and Phytosphingosine bases (CER[EOH], CER[EOS] and CER[EOP], respectively), that are crucial for the formation of the epidermal barrier, conferring protection from environmental factors and preventing trans-epidermal water loss. Furthermore, a large number of ceramides, derivatives of the same sphingoid bases and various fatty acids, are produced by dermal and epidermal cells and perform signalling roles in cell functions ranging from differentiation to apoptosis.Supplementation with the n-3 polyunsaturated fatty acids (PUFA) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have shown promise as therapeutic agents in a number of inflammatory skin conditions, altering the lipid profile of the skin and production of bioactive lipids such as the eicosanoids, docosanoids and endocannabinoids. In this study we wished to investigate whether EPA and DHA could also affect the ceramide profile in epidermis and dermis, and, in this way, contribute to formation of a robust lipid barrier and ceramide-mediated regulation of skin functions.Ex vivo skin explants were cultured for 6 days, and supplemented with EPA or DHA (50 μM). Liquid chromatography coupled to tandem mass spectrometry with electrospray ionisation was used to assess the prevalence of 321 individual ceramide species, and a number of sphingoid bases, phosphorylated sphingoid bases, and phosphorylated ceramides, within the dermis and epidermis.EPA augmented dermal production of members of the ceramide families containing Non-hydroxy fatty acids and Sphingosine or Dihydrosphingosine bases (CER[NS] and CER[NDS], respectively), while epidermal CER[EOH], CER[EOS] and CER[EOP] ceramides were not affected. DHA did not significantly affect ceramide production. Ceramide-1-phosphate levels in the epidermis, but not the dermis, increased in response to EPA, but not DHA.This ex vivo study shows that dietary supplementation with EPA has the potential to alter the ceramide profile of the skin, and this may contribute to its anti-inflammatory profile. This has implications for formation of the epidermal lipid barrier, and signalling pathways within the skin mediated by ceramides and other sphingolipid species. This article is part of a Special Issue entitled: Membrane Lipid Therapy: Drugs Targeting Biomembranes edited by Pablo V. Escribá.

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“…A recent exploratory study by our group examined cutaneous endocannabinoid and NAE levels in skin biopsies taken 24 hours after UVR exposure to a localized area of the buttock, and found no alteration. 50 However, that study employed only a single exposure of 2xMED of principally UVB (275-380, peak 305nm) implying that repeated UVR exposures may be necessary for endocannabinoid and NAE responses. In-keeping with this hypothesis, Magina et al detected changes in plasma endocannabinoids after six weeks of whole-body narrowband UVB (311nm) therapy.…”

Section: This Study Makes a Novel Examination Of Healthy Human In Vivmentioning

confidence: 98%

Serum endocannabinoids and N-acyl ethanolamines and the influence of simulated solar UVR exposure in humans in vivo

Felton

Kendall

Almaedani

et al. 2017

Photochem Photobiol Sci

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Solar ultraviolet radiation (UVR) exposure of human skin has beneficial and harmful effects on health, including impact on immune function, inflammation and reportedly mood, but these are not fully elucidated. Since the endocannabinoid system is implicated in many activities including mood alteration, our objective was to (i) determine and quantify circulating levels of a wide range of endocannabinoid and N-acyl ethanolamine (NAE) species (ii) evaluate whether these are modulated by cutaneous UVR exposures, as attained through repeated low level summer sunlight exposure. Wearing goggles to prevent eye exposure, 16 healthy volunteers (23-59y; 10 light skin, phototype II, and 6 dark skin, phototype V) received the same UVR exposures (1.3 SED, 95%UVA/5% UVB) thrice weekly for 6 weeks, whilst casually dressed to expose ~35% skin surface area. Blood samples were taken at baseline, days 1, 3 and 5 of week one, then at weekly intervals, and analysed by LC-MS/MS. Eleven endocannabinoids and NAEs were detected and quantified at baseline, with Npalmitoyl ethanolamine the most abundant (30% of total). Levels did not vary according to phototype (p>0.05), except for the NAE docosapentaenoyl ethanolamide, which was higher in phototype II than V (p=0.0002). Level of the endocannabinoid, 2-AG, was elevated during the UVR exposure course (p<0.05 vs baseline for all subjects; p<0.01 for each phototype group), with maximum levels reached by week 2-3, while NAE species did not significantly alter. These findings suggest differential involvement of the cutaneous endocannabinoid system in low dose solar UVR responses in humans.3

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N ‐Acyl ethanolamide and eicosanoid involvement in irritant dermatitis

Abstract: The differential bioactive lipid upregulation implicates their involvement in skin irritant responses, potentially reflecting roles in inflammatory cell recruitment and subsequent resolution of inflammation, giving scope for new treatment approaches to irritant dermatitis.

Cited by 27 publications

References 68 publications

Effect of oral eicosapentaenoic acid on epidermal Langerhans cell numbers and PGD₂ production in UVR‐exposed human skin: a randomised controlled study

Effect of oral eicosapentaenoic acid on epidermal Langerhans cell numbers and PGD₂ production in UVR‐exposed human skin: a randomised controlled study

Lipid functions in skin: Differential effects of n-3 polyunsaturated fatty acids on cutaneous ceramides, in a human skin organ culture model

Serum endocannabinoids and N-acyl ethanolamines and the influence of simulated solar UVR exposure in humans in vivo

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N ‐Acyl ethanolamide and eicosanoid involvement in irritant dermatitis

Abstract: The differential bioactive lipid upregulation implicates their involvement in skin irritant responses, potentially reflecting roles in inflammatory cell recruitment and subsequent resolution of inflammation, giving scope for new treatment approaches to irritant dermatitis.

Cited by 27 publications

References 68 publications

Effect of oral eicosapentaenoic acid on epidermal Langerhans cell numbers and PGD2 production in UVR‐exposed human skin: a randomised controlled study

Effect of oral eicosapentaenoic acid on epidermal Langerhans cell numbers and PGD2 production in UVR‐exposed human skin: a randomised controlled study

Lipid functions in skin: Differential effects of n-3 polyunsaturated fatty acids on cutaneous ceramides, in a human skin organ culture model

Serum endocannabinoids and N-acyl ethanolamines and the influence of simulated solar UVR exposure in humans in vivo

Contact Info

Product

Resources

About

Effect of oral eicosapentaenoic acid on epidermal Langerhans cell numbers and PGD₂ production in UVR‐exposed human skin: a randomised controlled study

Effect of oral eicosapentaenoic acid on epidermal Langerhans cell numbers and PGD₂ production in UVR‐exposed human skin: a randomised controlled study