Abstract
Ceramides are the major lipid constituent of lamellar sheets present in the intercellular spaces of the stratum corneum. These lamellar sheets are thought to provide the barrier property of the epidermis. It is generally accepted that the intercellular lipid domain is composed of approximately equimolar concentrations of free fatty acids, cholesterol, and ceramides. Ceramides are a structurally heterogeneous and complex group of sphingolipids containing derivatives of sphingosine bases in amide linkage with a variety of fatty acids. Differences in chain length, type and extent of hydroxylation, saturation etc. are responsible for the heterogeneity of the epidermal sphingolipids.
It is well known that ceramides play an essential role in structuring and maintaining the water permeability barrier function of the skin. In conjunction with the other stratum corneum lipids, they form ordered structures. An essential factor is the physical state of the lipid chains in the nonpolar regions of the bilayers. The stratum corneum intercellular lipid lamellae, the aliphatic chains in the ceramides and the fatty acids are mostly straight long-chain saturated compounds with a high melting point and a small polar head group. This means that at physiological temperatures, the lipid chains are mostly in a solid crystalline or gel state, which exhibits low lateral diffusional properties and is less permeable than the state of liquid crystalline membranes, which are present at higher temperatures.
The link between skin disorders and changes in barrier lipid composition, especially in ceramides, is difficult to prove because of the many variables involved. However, most skin disorders that have a diminished barrier function present a decrease in total ceramide content with some differences in the ceramide pattern.
Formulations containing lipids identical to those in skin and, in particular, some ceramide supplementation could improve disturbed skin conditions. Incomplete lipid mixtures yield abnormal lamellar body contents, and disorder intercellular lamellae, whereas complete lipid mixtures result in normal lamellar bodies and intercellular bilayers. The utilization of physiological lipids according to these parameters have potential as new forms of topical therapy for dermatoses. An alternative strategy to improving barrier function by topical application of the various mature lipid species is to enhance the natural lipid-synthetic capability of the epidermis through the topical delivery of lipid precursors.












Similar content being viewed by others
References
Roseman S. The synthesis of complex carbohydrates by multiglycotransferease systems and their potential function in intercellular adhesion. Chem Phys Lipids 1970; 5: 270–297
Rapport MM, Graf L. Inmunochemical reactions of lipids. Prog Allergy 1969; 13: 273–331
Harouse JM, Bhat S, Spitalnik SL, et al. Inhibition of entry of HIV-1 in neutral cell lines by antibodies against galactosyl ceramide. Science 1992; 253: 320–322
Nilsson G. Carbohydrate antigens in human lung carcinoma. APMIS Suppl 1992; 27: 149–161
Saito T, Ochiai H. Evidence for a glycolipid anchor of gp64, a putative cell-cell adhesion protein of Polysphondylium pallidum. Eur J Biochem 1993; 218: 623–628
Wiegandt H. Insect glycolipids. Biochim Biophys Acta 1992; 1123: 117–126
Curatolo W. Thermal behavior of fractionated and unfractionated bovine brain cerebrosides. Biochemistry 1982; 21: 1761–1772
Hoekstra D, Kok JW. Trafficking of glycosphingolipids in eukaryotic cells: sorting and recycling of lipids. Biochim Biophys Acta 1992; 1113: 277–294
Jeckel D, Karrenbauer A, Birk R, et al. Glucosylceramide is synthesized at the cytosolic surface of various Golgi subfractions. FEBS Lett 1990; 261: 155–157
Schutze SW, Potthof K, Machleidt T, et al. TNF activates NF-κB by phosphatidylcholine-specific phospholipase C-induced “acidic” sphingomyelin breakdown. Cell 1992; 71: 765–776
Kim MY, Linardic C, Obeid L, et al. Identification of sphingomyelin turnover as an effector mechanism for the action of tumor necrosis factor alpha and gammainterferon. J Biol Chem 1991; 266: 484–489
Okazaki T, Bell RM, Hannun YA. Sphingomyelin turnover induced by vitamin D3 in HL-60 cells: role in cell differentiation. 1989; 264: 19076–19080
Okazaki T, Bielawaski A, Bell RM, et al. Role of ceramide as lipid mediator of 1a, 25-dihydroxyvitamin D3-induced HL-60 cell differentiation. J Biol Chem 1990; 265: 15823–15831
Dobrowski RT, Hannun YA. Ceramide activates a cytosolic phosphatase. J Biol Chem 1992; 267: 5048–5051
Goldkorn T, Dressler KA, Muindi J, et al. Ceramide stimulates epidermal growth factor receptor phosphorylation in A431 human epidermoid carcinoma cells: evidence that ceramide may mediate sphingosine action. J Biol Chem 1991; 266: 16092–16097
Obeid LM, Linardic CM, Karolak LA, et al. Programmed cell death induced by ceramide. Science 1993; 259: 1769–1771
Kalen A, Borchardt RA, Bell RM. Elevated ceramide levels in GH4C1 cells treated with retinoic acid. Biochim Biophys Acta 1992; 1125: 90–96
Pagano RE. The Golgi apparatus: insights from lipid biochemistry. Biochem Soc Trans 1990; 18: 361–366
Rosenwald AG, Pagano RE. Inhibition of glycoprotein traffic through the secretory pathway by ceramide. J Biol Chem 1993; 268: 4577–4579
Joseph CK, Byun HS, Bittman R, et al. Substrate recognition by ceramide-activated protein kinase. J Biol Chem 1993; 268: 20002–20006
Raines MA, Kolesnick RN, Golde DW. Sphingomyelinase and ceramide activate mitogen-activated protein-kinase. J Biol Chem 1993; 268: 14572–14575
Dobrowsky RT, Hannun YA. Ceramide-activated protein phosphatase: partial purification and relationship to protein phosphatase 2 A. Adv Lipid Res 1993; 25: 91–104
Dobrowsky RT, Kamibayashi C, Mumby MC, et al. Ceramide activates heterotrimetric protein phosphatase 2 A. J Biol Chem 1993; 268: 15523–15530
Geilen CC, Barz S, Bektas M. Sphingolipid signaling in epidermal homeostasis. Skin Pharmacol Appl Skin Physiol 2001; 14: 261–271
Elias PM, Friend DS. The permeability barrier in mammalian epidermis. J Cell Biol 1975; 65: 180–191
Elias PM, Goerke J, Friend DS. Mammalian epidermal barrier lipid layers: composition and influence on structure. J Invest Dermatol 1977; 69: 535–546
Elias PM. Epidermal lipids, barrier function, and desquamation. J Invest Dermatol 1983; 80: 44–49
Landmann L. The epidermal permeability barrier. Anat Embryol (Berl) 1988; 178: 1–10
Swartzenruber DC, Wertz PW, Madison KC, et al. Evidence that the corneocyte has a chemically bound lipid envelope. J Invest Dermatol 1987; 88: 709–713
Wertz PW, Downing DT. Covalently bound ω-hydroxyacylsphingosine in the stratum corneum. Biochim Biophys Acta 1987; 917: 108–111
Steven AC, Steinert PM. Protein composition of cornified cell envelopes of epidermal keratinocytes. J Cell Sci 1994; 107: 693–700
Elias PM, Menon GK. Structural and lipid biochemical correlates of the epidermal permeability barrier. Adv Lipid Res 1991; 24: 1–26
Friberg SE, Kayali I, Rhein LD, et al. The importance of lipids for water uptake in stratum corneum. Int J Cosmet Sci 1990; 12: 5–12
Schürer NY, Plewig G, Elias PM. Stratum corneum lipid function. Dermatologica 1991; 183: 77–94
Fartasch M. The nature of the epidermal barrier: structural aspects. Adv Drug Deliv Rev 1996; 18: 273–282
Rawlings AV, Scott IR, Harding CR, et al. Stratum corneum moisturisation at molecular level. J Invest Dermatol 1994; 103: 731–740
Elias PM, Feingold KR. Lipids and the epidermal water barrier: metabolism, regulation and pathophysiology. Semin Dermatol 1992; 11: 176–182
Menon GK, Feingold KR, Elias PM. The lamellar body secretory response to barrier disruption. J Invest Dermatol 1992; 98: 279–289
Fartasch M, Bassukas ID, Diepgen TH. Structural relationship between epidermal lipid lamellae, lamellar bodies and desmosomes in human epidermis: an ultrastructural study. Br J Dermatol 1993; 128: 1–9
Elias PM. The role of biological lipids in skin conditioning. In: Schueller R, Romanowski P, editors. Conditioning agents for hair and skin. New York: Marcel Dekker, 1999: 35–55
Mao-Quiang M, Jain M, Feingold KR, et al. Secretory phospholipase A2 activity is required for permeability barrier homeostasis. J Invest Dermatol 1996; 106: 57–63
Holleran WM, Ginns EI, Menon GK, et al. Consequences of beta-glucocerebrosidase deficiency in epidermis: ultrastructure and permeability barrier alterations in Gaucher disease. J Clin Invest 1994; 93: 1756–1764
Uchida Y, Hara M, Nishio H, et al. Epidermal sphingomyelins are precursors for selected stratum corneum ceramides. J Lipid Res 2000; 41: 2071–2082
Schmuth M, Mao-Quiang M, Weber F, et al. Permeability barrier disorder in Nieman-pick disease: sphingomyelin-ceramide processing required for normal barrier homeostasis. J Invest Dermatol 2000; 115: 459–466
Brooks G, Idson B. Skin lipids. Int J Cosmet Sci 1991; 13: 103–113
Schaefer H, Redelmeier TE. Skin barrier: principles of percutaneous absorption. Basel: Karger, 1996
Chang F, Swartzedrauber DC, Wertz PW, et al. Covalently bound lipids in keratinizing epithelia. Biochim Biophys Acta 1993; 1150: 98–102
Stewart ME, Downing DT. The ω-hydroxyceramides of pig epidermis are attached to corneocytes solely through ω-hydroxyl groups. J Lipid Res 2001; 42: 1105–1110
Meguro S, Arai Y, Masukawa Y, et al. Relationship between covalently bound ceramides and transepidermal water loss (TEWL). Arch Dermatol Res 2000; 292: 463–468
Elias PM, Fartasch M, Crumrine D, et al. Origin of the corneocyte lipid envelope (CLE): observations in harlequin Ichthyosis and cultured human keratinocytes. J Invest Dermatol 2000; 115: 765–769
Cullis PR, Hope MJ. Physical properties and functional roles of lipids in membranes. In: Vance DE, Vance JE, editors. Biochemistry of lipids and membranes. Menlo Park: Benjamin Cummings, 1985: 25–72
Davis J. The description of membrane lipid conformation, order and dynamics by 2H NMR. Biochim Biophys Acta 1983; 737: 117–171
Wertz PW, Downing DT. Epidermal lipids. In: Goldsmith LA, editor. Physiology, biochemistry and molecular biology of the skin. 2nd ed. Oxford: Oxford University Press, 1991: 205–235
Hedberg CL, Wertz PW, Downing DT. The time course of lipid biosynthesis in pig epidermis. J Invest Dermatol 1988; 91: 169–174
Feingold KR. The regulation and role of epidermal lipid synthesis. Adv Lipid Res 1991; 24: 57–82
Brod J. Characterization and physiological role of epidermal lipids. J Invest Dermatol 1991; 30: 84–90
Wertz PW, Miethke MC, Long SA, et al. The composition of the ceramides from human stratum corneum and from comedones. J Invest Dermatol 1985; 84: 410–412
Robson KJ, Stewart ME, Michelsen S, et al. 6-hydroxy-4-sphingenine in human epidermal ceramides. J Lipid Res 1994; 35: 2060–2068
Wertz PW, Downing DT. Ceramides of pig epidermis: structure determination. J Lipid Res 1983; 24: 759–765
Stewart ME, Downing DT. A new 6-hydroxy-4-sphingenine-containing ceramide in human skin. J Lipid Res 1999; 40: 1434–1439
Motta S, Monti M, Sesana S, et al. Ceramide composition of the psoriatic scale. Biochim Biophys Acta 1993; 1182: 147–151
Holleran WM, Mao-Quiang M, Gao WN, et al. Sphingolipids are required for mamalian epidermal barrier function: inhibition of sphingolipid synthesis delays barrier recovery after acute perturbation. J Clin Invest 1991; 88: 1338–1345
Imokawa G, Akasaki S, Minematsu Y, et al. Importance of intercellular lipids in water-retention properties of the stratum corneum: induction and recovery study of surfactant dry skin. Arch Dermatol Res 1989; 281: 45–51
Wertz PW. The nature of epidermal barrier: biochemical aspects. Adv Drug Deliv Rev 1996; 18: 283–294
Schürer NY, Elias PM. The Biochemistry and function of stratum corneum lipids. Adv Lipid Res 1991; 24: 27–56
Kerscher M, Korting HC, Scharfer-Korting M. Skin ceramides: structure and function. Eur J Dermatol 1991; 1: 39–43
Farin F, Lambers H, Keuning W, et al. Human skin identical ceramides. Cosmet Toiletries 1995; 3: 126–132
Bouwstra JA, Gooris GS, Van der Speck JA, et al. The lipid and protein structure of mouse stratum corneum: a wide and small angle diffraction study. Biochem Biophys Acta 1994; 1212: 183–192
Forslind B. A domain mosaic model of the skin barrier. Acta Dermatol Venereol 1994; 74: 1–6
Forslind B. A new look at the skin barrier: a biophysical and mechanical model for barrier function. J Appl Cosmetol 1994; 12: 63–72
Forslind B, Engström S, Engblom J, et al. A novel approach to the understanding of human skin barrier function. J Dermatol Sci 1997; 14: 115–125
White SH, Mirejovsky D, King GI. Structure of lamellar lipid domains and corneocyte envelopes of murine stratum corneum: an X-ray diffraction study. Biochemistry 1988; 27: 3725–3732
McIntosh TJ, Stewart ME, Downing ET. X-ray diffraction of isolated skin lipids: reconstitution of intercellular lipid domains. Biochemistry 1996; 35: 3649–3653
Bouwstra JA, Thewalt J, Gooris GS, et al. A model membrane approach to the epidermal permeability barrier: an X-ray diffraction study. Biochemistry 1997; 36: 7717–7725
Shah J, Atienza JM, Rawlings AV, et al. Physical properties of ceramides: effect of fatty acid hydroxylation. J Lipid Res 1995; 36: 1945–1955
Bouwstra JA, Pilgram G, Gooris G, et al. New aspects of the skin barrier organization. Skin Pharmacol Appl Skin Physiol 2001; 14 Suppl. 1: 52–62
Bouwstra JA. The skin barrier, a well-organized membrane. Colloids Surf A: Physicochem Eng Asp 1997; 123–124: 403–413
López O, Cócera M, Campos L, et al. Use of wide and small angle X-ray diffraction to study the modifications in the stratum corneum induced by octyl glucoside. Colloids Surf A: Physicochem Eng Asp 2000; 162: 123–130
Pilgram GS, Engelsma-van Pelt AM, Oostergetel GT, et al. Study on the lipid organisation of stratum corneum lipid models by (cryo) electron diffraction. J Lipid Res 1998; 39: 1669–1676
Pilgram GS, Engelsma-van Pelt AM, Bouwstra JA, et al. Electron diffraction provides new information on human stratum corneum lipid organisation studied in relation to depth and temperature. J Invest Dermatol 1999; 133: 403–409
Swartzenruber DC, Wertz PW, Kitko DJ, et al. Molecular models of intercellular lipid lamellae in mamalian stratum corneum. J Invest Dermatol 1989; 92: 251–257
Caputo R, Gasparini G. The freeze fracture replication technique in studies of skin. In: Skerrow CJ, editor. Methods in skin research. Chichester: Wiley, 1985: 37–70
López O, Cócera M, Walter P, et al. Octyl glucoside as a tool to induce structural modifications in the stratum corneum. Colloids Surf A 2000; 168: 115–123
Abraham W, Downing DT. Lamellar structures formed by stratum corneum lipids in vitro: a deuterium nuclear magnetic resonance (NMR) study. Pharmacol Res 1992; 9: 1415–1421
Kitson N, Thewalt J, Lafleur M, et al. A model membrane approach to the epidermal permeability barrier. Biochemistry 1994; 33: 6707–6715
White R, Walker M. Thermotropic and lyotropic behaviour of epidermal lipid fractions. Biochem Soc Trans 1980; 18: 881–882
Grotenhuis ET, Demel RA, Ponec M, et al. Phase behavior of stratum corneum lipids in mixed Langmuir-Blodgett monolayers. Biophys J 1996; 71: 1389–1399
Sparr E, Eriksson L, Bouwstra JA. AFM study of lipid monolayers: III phase behaviour of ceramides, cholesterol and fatty acids. Langmuir 2001; 17: 164–172
Moore DJ, Rerek ME, Mendelsohn R. Lipid domains and orthorombic phases in model stratum corneum: evidence from Fourier transform infrared spectroscopy studies. Biochem Biophys Res Commun 1997; 231: 797–801
Moore DJ, Rerek ME, Mendelsohn R. FTIR spectroscopy studies of the conformational order and phase behaviour ceramides. J Phys Chem 1997; 101: 8933–8940
Moore DJ, Rerek ME, Mendelsohn R. Role of ceramides 2 and 5 in the structure of the stratum corneum lipid barrier. Int J Cosmet Sci 1999; 21: 353–368
Chen HC, Mendelson R, Rerek ME, et al. Fourier transform infrared spectroscopy and differential scanning calorimetry studies of fatty acid homogeneous ceramide 2. Biochim Biophys Acta 2000; 1468: 293–303
Chen HC, Mendelson R, Rerek ME, et al. Effect of cholesterol on miscibility and phase behavior in binary mixtures with synthetic ceramide 2 and octadecanoic acid: infrared studies. Biochim Biophys Acta 2001; 1512: 345–356
Bouwstra JA, Gooris GS, Salomonsde Vries MA, et al. Structure of human stratum corneum as a function of temperature and hydration: a wide-angle X-ray diffraction study. Int J Pharm 1992; 84: 205–216
Bouwstra JA, Gooris GS, van der Spek JA, et al. The structure of human stratum corneum as determined by small angle X-ray scattering. J Invest Dermatol 1991; 96: 1006–1014
Bouwstra JA, Gooris GS, Dubbelaar FER, et al. Role of ceramide 1 in the molecular organization of the stratum corneum lipids. J Lipid Res 1998; 39: 186–196
Imokava G, Abe A, Jin K, et al. Decreased level of ceramides in stratum corneum of atopic dermatitis: an etiologic factor in atopic dry skin. J Invest Dermatol 1991; 96: 523–526
Lavrijsen APM, Bouwstra JA, Gooris GS, et al. Reduced skin barrier function parallels abnormal stratum corneum lipid organisation in patients with lamellar ichthyosis. J Invest Dermatol 1995; 105: 619–624
Gay CL, Guy RH, Golden GM, et al. Characterization of low-temperature (i.e. <65°C) lipid transitions in human stratum corneum. J Invest Dermatol 1994; 103: 233–239
Golden GM, Guzek DB, Harris RR, et al. Lipid thermotropic transitions in human stratum corneum. J Invest Derm 1986; 86: 255–259
Golden GM, McKie JE, Potts RO. Role of stratum corneum lipid fluidity in transdermal drug flux. J Pharm Sci 1987; 76: 25–28
Naik A, Guy RH. Infrared spectroscopy and differential scanning calorimetry investigations of the human stratum corneum barrier function. In: Potts RO, Guy RH, editors. Mechanisms of transdermal drug delivery. New York: Marcel Dekker, 1997: 87–162
Moore DJ, Rerek ME. Recent biophysical studies of ceramides and their role in skin barrier function. Proc Cosmet Sci Conf 2000; 1: 36–43
López O, Cócera M, Parra JL, et al. Influence of ceramides in the solubilization of stratum corneum lipid liposomes by C12-betaine/sodium dodecyl sulfate mixtures. Int J Pharm 1999; 187: 231–241
Petersen RD. Ceramides: key components for skin protection. Cosmet Toiletries 1992; 107: 45–49
Thestrup-Pedersen K. How common are skin barrier problems? Yamanouchi Satellite Symposium 4th EADV Congress. Clinical Management of Skin Barrier Problems; 1995 Oct 10–15; Brussels, 5–8
De Paepe K. Evaluation of the efficacy of dermato-cosmetic products [PhD thesis]. Brussels: Vrije Universiteit Brussel, 2001
Lampe MA, Burlingame AL, Whitney J, et al. Human stratum corneum lipids: characterization and regional variations. J Lipid Res 1983; 24: 120–150
Ghadially RG, Brown BE, Sequeira-Martín SM, et al. The aged epidermal permeability barrier: structural, functional and lipid biochemical abnormalities in humans and a senescent murine model. J Clin Invest 1995; 95: 2281–2290
Denda M, Koyama J, Hori J, et al. Age- and sex-dependent change in stratum corneum sphingolipids. Arch Dermatol Res 1993; 285: 415–417
Wefers H, Melnik BC, Flür M, et al. Influence of UV irradiation on the composition of human SC lipids. J Invest Dermatol 1991; 96: 959–962
Conti A, Rogers J, Verdejo P, et al. Seasonal influences on stratum corneum ceramide 1 fatty acids and the influence of topical essential fatty acids. Int J Cosmet Sci 1996; 18: 1–12
Motta S, Monti M, Sesana S, et al. Abnormality of water barrier function in psoriasis: role of ceramide fractions. Arch Dermatol 1994; 130: 452–456
Wertz PW, Cox PS, Squier CA, et al. Lipids of epidermis and keratinized and non-keratinized oral epithelia. Comp Biochem Physiol B 1986; 83: 529–531
Wertz PW, Kremer M, Squier SM. Comparison of lipids from epidermal and palatal stratum corneum. J Invest Dermatol 1992; 98: 375–378
Saint-Léger D, François AM, Lévêque JL, et al. Age-associated changes in stratum corneum lipids and their relation to dryness. Dermatologica 1988; 177: 159–164
Rawlings AV, Rogers J, Mayo AM. Changes in lipids in the skin aging process. Biocosmet Skin Aging 1993; 1: 31–45
Rogers J, Harding C, Mayo A, et al. Stratum corneum lipids: the effect of ageing and the seasons. Arch Dermatol Res 1996; 288: 765–770
Jin K, Higaki Y, Takagi Y, et al. Analysis of beta-glucocerebrosidase and ceramidase activities in atopic and aged dry skin. Acta Derm Venereol 1994; 74: 337–340
Yamamura T, Tezuka T. Change in sphingomyelinase activity in human epidermis during ageing. J Dermatol Sci 1990; 1: 79–84
Fartasch M, Bassukas ID, Diepgen T. Disturbed extruding mechanism of lamellar bodies in dry non-eczematous skin of atopics. Br J Dermatol 1992; 127: 221–227
Yoshikawa N, Imokawa G, Akimoto K, et al. Regional analysis of ceramides within the stratum corneum in relation to seasonal changes. Dermatology 1994; 188: 207–214
Rawlings A, Hope J, Rogers J, et al. Abnormalities in stratum corneum structure, lipid composition and desmosome degradation in soap induced winter xerosis. J Soc Cosmet Chem 1994; 45: 203–220
Burr G, Burr M. A new deficiency disease produced by rigid exclusion of fat from diet. J Biol Chem 1929; 82: 345–367
Hou S, White S, Menon G, et al. Membrane structures in normal and essential fatty acid deficient stratum corneum: characteristics by ruthenium tetroxide staining and x-ray diffraction. J Invest Dermatol 1991; 96: 216–223
Yumamoto A, Serizawa M, Ito M, et al. Stratum corneum lipid abnormalities in atopic dermatitis. Arch Dermatol Res 1991; 283: 219–223
Brod J, Traitler H, Studer A, et al. Evolution of lipid composition in kin treated with blackcurrant seed oil. Int J Cosmet Sci 1988; 10: 149–159
Schreiner V, Gooris GS, Pfeiffer S, et al. Barrier characteristics of different human skin types investigated with X-Ray diffraction, lipid analysis and Electron Microscopy Imaging. J Invest Dermatol 2000; 114: 654–660
Kompaore F, Dupont C, Marty JP. In vivo evaluation in man by two-invasive methods of the stratum corneum barrier function after physical and chemical modification. Int J Cosmet Sci 1991; 13: 293–302
Elias PM, Ansel JC, Wood LC, et al. Signalling networks in barrier homeostasis: the mystery widens. Arch Dermatol 1996; 132: 1505–1506
Grubauer G, Feingold KR, Elias PM. Relationship of epidermal lipogenesis to cutaneous barrier function. J Lipid Res 1987; 28: 746–752
Holleran WM, Gao WN, Feingold KR, et al. Localisation of epidermal sphingolipid synthesis and serine palmitoyl transferase activity: alterations imposed by permeability requirements. Arch Dermatol Res 1995; 287: 254–258
Feingold KR. Permeability barrier homeostasis, its biochemical basis and regulation. Cosmet Toiletries 1997; 112: 49–59
López O, Walter P, Cócera M, et al. Structural modifications in the stratum corneum by effect of different solubilizing agents: a study based on high-resolution lowtemperature scanning electron microscopy. Skin Pharmacol Appl Skin Physiol 2000; 13: 265–272
Fulmer AW, Kramer GJ. Stratum corneum lipid abnormalities in surfactant-induced dry scaly skin. J Invest Dermatol 1986; 86: 598–602
Treffel P, Gabard B. Measurement of sodium lauryl sulfate skin irritation. Acta Derm Venereol 1996; 76: 341–343
Di Nardo A, Sugino K, Wertz P, et al. Sodium lauryl sulfate (SLS) induced irritant contact dermatitis: a correlation study between ceramides and in vivo parameters of irritation. Contact Dermatitis 1996; 35: 86–91
Di Nardo A, Sugino K, Ademola J, et al. Role of ceramides in proclivity to toluene and xylene-induced skin irritation in man. Derm Beruf Umwelt 1996; 44: 119–125
Berardesca E, Anderson PH, Bjerring P, et al. Erythema induced by organic solvents: in vivo evaluation of oxygenized and deoxygenated hemoglobin by reflectance spectroscopy. Contact Dermatitis 1992; 27: 8–11
Jacobs G, Castellazi A, Dierickx PJ. Evaluation of a non-invasive human and in vitro cytotoxicity method as alternatives to the skin irritation test on rabbit. Contact Derm 1989; 21: 239–244
Wahlberg JE. Erythema-inducing effects of solvents following topical administrations. Derm Beruf Umwelt 1984; 32: 91–94
Grubauer G, Feingold KR, Harris RM, et al. Lipid content and lipid type as determinant of the epidermis permeability barrier. J Lipid Res 1989; 30: 89–96
Proksch E, Feingold KR, Mao-Qiang M, et al. Barrier function regulates epidermal DNA synthesis. J Invest Dermatol 1991; 87: 1668–1673
Motta S, Sesana S, Monti M, et al. Interlamellar lipid differences between normal and psoriatic stratum corneum. Acta Derm Venereol Suppl (Stockh) 1994; 186: 131–132
Ilzuka H, Ishida-Yamamoto A, Honda H. Epidermal remodelling in psoriasis. Br J Dermatol 1996; 135: 433–438
Fartasch M. Epidermal barrier in disorders of the skin. Microsc Res Tech 1997; 38: 361–372
Alessandrini F, Stachowitz S, Ring J, et al. The level of prosaposin is decreased in the skin of patients with psoriasis vulgaris. J Invest Dermatol 2001; 116: 394–400
Werner Y, Lindberg M, Forslind B. Membrane-coating granules in “dry” noneczematous skin of patients with atopic dermatitis. Acta Derm Venereol 1987; 67: 385–390
Melnik B, Hollman J, Plewig G. Decreased stratum corneum ceramides in atopic individuals: a patobiochemical factor in xerosis. Br J Dermatol 1988; 119: 547–549
Melnik B, Hollman J, Hofmann U. Lipid composition of outer stratum corneum and nails in atopic and control subjects. Arch Dermatol Res 1990; 282: 549–551
Imokawa G, Abe A, Jin K, et al. Decreased level of ceramides in stratum corneum of atopic dermatitis: and etiologic factor in atopic dry skin? J Invest Dermatol 1991; 96: 523–526
Yamamoto A, Serizawa S, Ito M, et al. Stratum corneum lipid abnormalities in atopic dermatitis. Arch Dermatol Res 1991; 238: 219–223
Murata Y, Ogata J, Higaki Y, et al. Abnormal expression of sphingomyelin acylase in atopic dermatitis: an etiologic factor for ceramide deficiency? J Invest Dermatol 1996; 106: 1242–1249
Di Nardo A, Wertz P, Giannetti A, et al. Ceramide and cholesterol composition of the skin of patients with atopic dermatitis. Acta Derm Venereol (Stockh) 1998; 78: 27–30
Williams ML. Lipids in normal and pathological desquamation. In: Elias PM, editor. Advances in lipid research. Vol 24. San Diego (CA): Academic Press, 1991: 211–262
Paige DG, Morse-Fischer N, Harper JI. Quantification of stratum corneum ceramides and lipid envelope ceramides in the hereditary ichthyoses. Br J Dermatol 1994; 131: 23–27
Hamanaka S, Ujihara M, Serizawa S, et al. A case of recessive X-linked ichthyosis: scale-specific abnormalities of lipid composition may explain the pathogenesis of the skin manifestation. J Dermatol 1997; 24: 156–160
Berra B, Adorni L, Ciuffo R, et al. Skin lipid abnormalities in Gaucher’s disease. J Appl Cosmetol 2000; 18: 113–123
Jensen JM, Schütze S, Neumann C, et al. Impaired cutaneous permeability barrier function, skin hydration and sphingomyelinase activity on Keratin 10 deficient mice. J Invest Dermatol 2000; 115: 708–713
Saint-Léger D, François AM, Lévêque JL, et al. Stratum corneum lipids in skin xerosis. Dermatologica 1989; 178: 151–155
Akimoto K, Yoshikawa N, Higaki Y, et al. Quantitative analyses of stratum corneum lipids in xerosis and asteatotic eczema. J Dermatol 1993; 20: 1–6
Berardesca E, Fideli D, Borroni G, et al. In vivo hydration and water retention capacity of stratum corneum in clinically uninvolved skin in atopic and psoriatic patients. Acta Derm Venereol (Stockh) 1990; 70: 400–404
Sedenari S, Giusti G. Objective assessment of the skin of children affected by atopic dermatitis: a study on pH, capacitance and TEWL in eczematous and clinically uninvolved skin. Acta Derm Venereol (Stockh) 1995; 75: 429–433
Matsumoto M, Umemoto N, Sugiura H, et al. Difference in ceramide composition between “dry” and “normal” skin patients with atopic dermatitis. Acta Derm Venereol (Stockh) 1999; 79: 246–247
Ghadially R, Williams ML, Hou SYE, et al. Membrane structural abnormalities in the stratum corneum of the autosomal recessive ichthyosis. J Invest Dermatol 1992; 99: 755–763
Tupker RA, Pinagoda J, Coenraads PJ, et al. Susceptibility to irritants: role of barrier function, skin dryness and history of atopic dermatitis. Br J Dermatol 1990; 123: 199–205
Downing DT, Stewart ME, Wertz PW, et al. Essential fatty acids and acne. J Am Acad Dermatol 1986; 14: 221–225
Perisho K, Wertz PW, Madison KC, et al. Fatty acids of acylceramides from comedones and from the skin surface of acne patients and control subjects. J Invest Dermatol 1988; 90: 350–353
Berardesca E, Vignoli GP, Oresajo C, et al. Prevention of barrier function damage by topically applied ceramides. Proceedings of the 17th IFSCC International Congress; 1992 Oct 13–16; Yokohama, 881–888
Mao-Quiang M, Feingold KR, Elias PM. Exogenous lipids influence permeability barrier recovery in acetone-treated murine skin. Arch Dermatol 1993; 129: 728–738
Yang L, Mao-Quiang M, Taljebini M, et al. Topical stratum corneum lipids accelerate barrier repair after tape stripping, solvent treatment and some but not all types of detergent treatment. Br J Dermatol 1995; 133: 679–685
Mao-Quiang M, Feingold KR, Thornfeldt CR, et al. Optimization of physiological lipid mixtures for barrier repair. J Invest Dermatol 1996; 106: 1096–1101
Mao-Quiang M, Feingold KR, Wang F, et al. A natural lipid mixture improves barrier function and hydration in human and murine skin. J Soc Cosmet Chem 1997; 47: 157–166
Linter K, Mondon P, Girard F, et al. The effect of synthetic ceramide-2 on transepidermal water loss after stripping or SLS treatment: an in vivo study. Int J Cosmet Sci 1997; 19: 15–25
López O, Cócera M, Walter P, et al. Effect of liposomes on delipidized stratum corneum structure: an “in vitro” study based on high resolution low temperature scanning electron microscopy. Colloids Surf A: Physiochem Eng Asp 2001; 182: 35–42
De Paepe K, Derde MP, Roseeuww D, et al. Incorporation of Ceramide 3B in dermatocosmetic emulsions: effect on the TEWL of SLS-damaged skin. J Eur Acad Dermatol Venereol 2000; 14: 272–279
Imokawa G, Akasaki S, Hattori M, et al. Selective recovery of deranged waterholding properties by stratum corneum lipids. J Invest Dermatol 1986; 87: 758–761
Imokawa G, Akasaki S, Kawamata A, et al. Water-retaining function in the stratum corneum and its recovery properties by synthetic pseudoceramides. J Soc Cosmet Chem 1989; 40: 273–285
De Paepe K, Vandamme P, Derde MP, et al. Body lotions enriched with skin identical lipids: a TEWL study of aged skin and SLS-induced scaly skin. Euro Cosmetics 1999; 7: 38–45
De Paepe K, Roseeuw D, Rogiers V. Repair of acetone and SLS damaged human skin barrier function by topically applied emulsions containing barrier lipids. J Eur Acad Dermatol Venereol 2002; 16: 587–594
Rodrigues L, Amores da Silva P, Pinto P, et al. Identification of the in vivo topically applied “human-identical” ceramides included in negatively charged liposomes. Boll Chim Farma 1998; 137: 395–402
De Paepe K, Roseeuw D, Rogiers V. Effect of ceramides-containing lotions on the barrier function of the skin. In: Conference proceedings, active ingredients. Tunbridge Wells: Step Publishing, 1998: 121–132
de Pera M, Coderch L, Fonollosa J, et al. Effect of internal wool lipid liposomes on skin repair. Skin Pharmacol Appl Skin Physiol 2000; 13: 188–195
Coderch L, de Pera M, Fonollosa J, et al. Efficacy of stratum corneum lipid supplementation on human skin. Contact Dermatitis 2002; 47: 139–146
Hatziantoniou S, Rallis M, Demetzos C, et al. Pharmacological activity of natural lipids on a skin barrier disruption model. Pharmacol Res 2000; 42: 55–59
Schmid MH, Korting HC. Liposomes for atopic dry skin: the rationale for a promising approach. Clin Investig 1993; 71: 649–653
Korting HC, Zienicke H, Schäfer-Korting M, et al. Liposome encapsulation improve efficiency of betamethasone dipropionate in atopic eczema but not in psoriasis vulgaris. Eur J Clin Pharmacol 1990; 39: 349–351
Chamlin SL, Frieden IJ, Fowler A, et al. Ceramide-dominant, barrier-repair lipids improve childhood atopic dermatitis. Arch Dermatol 2001; 137: 1110–1112
Prottey C, Hartop PJ, Press M. Correction of the cutaneous manifestations of essential fatty acid deficiency in man by application of sunflower seed oil to the skin. J Invest Dermatol 1975; 64: 228–234
Fartasch M, Teal J, Menon GK. Mode of action of glycolic acid on human stratum corneum: ultrastructural and functional evaluation of the epidermal barrier. Arch Dermatol Res 1997; 289: 404–409
Rawlings AV, Davies A, Carlomusto M, et al. Effect of lactic acid isomers on keratinocyte ceramide synthesis, stratum corneum lipid levels and stratum corneum barrier function. Arch Dermatol Res 1996; 288: 383–390
Zhang K, Kosturko R, Rawlings AV. The effect of thiols on epidermal lipid biosynthesis [abstract]. J Invest Dermatol 1995; 104: 687
Carlomusto M, Pillai K, Rawlings AW. Human keratinocytes in vitro can utilise exogenously supplied sphingolipid analogues for keratinocyte ceramide biosynthesis [abstract]. J Invest Dermatol 1996; 106: 919
Davies A, Verdejo P, Feinberg C, et al. Increased stratum corneum ceramide levels and improved barrier function following treatment with tetracetylphytosphingosine. J Invest Dermatol 1996; 106: 918–1000
Spiegel S, Merrill AH. Sphingolipid metabolism and cell growth regulation. FASEB J 1996; 10: 1388–1397
Hunnan YA. Functions of ceramides in coordinating cellular responses to stress. Science 1996; 274: 1855–1859
Merrill AH, Schmelz EM, Dillehay DL, et al. Sphingolipids. Enigmatic lipid class: biochemistry, physiology and pathophysiology. Toxicol Appl Pharmacol 1997; 142: 208–225
Pillai K, Frew L, Cho S, et al. Synergy between the vitamin D precursor, 25 hydroxyvitamin D and short chain ceramides on human keratinocyte growth and differentiation. J Invest Dermatol Suppl 1996; 1: 39–45
Carlomusto M, Mahajan M, Pillai S. Vitamin D-mediated keratinocyte differentiation does not involve sphingomyelin hydrolysis [abstract]. J Invest Dermatol 1997; 108: 660
Tanno O, Ota Y, Kitamura N, et al. Nicotinamide increases biosynthesis of ceramides as well as other stratum corneum lipids to improve the epidermal permeability barrier. Br J Dermatol 2000; 143: 524–531
Ponec M, Weerheim A, Kempenaar J, et al. The formation of competent barrier lipids in reconstructed human epidermis requires the presence of vitamin C. J Invest Dermatol 1997; 109: 348–355
Marsh NN, Elias PM, Holleran WM. Glucosylceramides stimulate murine epidermal hyperproliferation. J Clin Invest 1995; 95: 2903–2909
Uchida Y, Iwamori M, Nagai Y. Activation of keratinisation of keratinocytes from fetal rat skin with N (lineoyl) ω-hydroxy fatty acyl sphingosyl glucose as a marker of epidermis. Biochim Biophys Res Commun 1990; 179: 162–168
Bosko C, Samares S, Santanastasio H, et al. Influence of fatty acid composition of acylceramides on keratinocyte differentiation [abstract]. J Invest Dermatol 1996; 106: 871
Harding CR, Watkinson A, Rawlings AV, et al. Dry skin, moisturization and corneodesmolysis. Int J Cosmet Sci 2000; 22: 21–52
Acknowledgements
We thank Ms C. Alonso, Dr M. Martí, and Mr G. von Knorring for their expert technical assistance. We are also indebted to Dr J. Notario (MD) and Professor J. Peiry (MD) from Servicio de Dermatología de la Ciudad Sanitaria y Universitaria de Bellvitge (Barcelona, Spain) for their useful comments.
No sources of funding were used to assist in the preparation of this manuscript. The authors have no conflicts of interest that are directly relevant to the content of this manuscript.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Coderch, L., López, O., de la Maza, A. et al. Ceramides and Skin Function. Am J Clin Dermatol 4, 107–129 (2003). https://doi.org/10.2165/00128071-200304020-00004
Published:
Issue Date:
DOI: https://doi.org/10.2165/00128071-200304020-00004