Skip to main content

Role of Ceramides in Barrier Function of Healthy and Diseased Skin

American Journal of Clinical Dermatology volume 6, pages 215–223 (2005)Cite this article

Abstract

Stratum corneum intercellular lipids play an important role in the regulation of skin water barrier homeostasis and water-holding capacity. Modification of intercellular lipid organization and composition may impair these properties. Patients with skin diseases such as atopic dermatitis, psoriasis, contact dermatitis, and some genetic disorders have diminished skin barrier function. Lipid composition in diseased skin is characterized by decreased levels of ceramide and altered ceramide profiles. To clarify mechanisms underlying ceramides as a causative factor of skin disease, investigators have examined the activity of enzymes in the stratum corneum on ceramide production and degradation. The activities of ceramidase, sphingomyelin deacylase, and glucosylceramide deacylase are increased in epidermal atopic dermatitis. Investigators have also compared the expression levels of sphingolipid activator protein in the epidermis of normal and diseased skin. A decreased level of prosaposin has been identified in both atopic dermatitis and psoriasis. These results indicate that decreased ceramide level is a major etiologic factor in skin diseases. Hence, topical skin lipid supplementation may provide opportunities for controlling ceramide deficiency and improving skin condition.

This is a preview of subscription content, access via your institution.

Access options

Buy single article

Instant access to the full article PDF.

USD 49.95

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Table I
Table II
Table III

References

  1. Bouwstra JA, Honeywell-Nguyen PL, Gooris GS, et al. Structure of the skin barrier and its modulation by vesicular formulations. Prog Lipid Res. 2003; 42: 1–36

    PubMed  Article  CAS  Google Scholar 

  2. Imokawa G, Abe A, Jin K, et al. Decreased level of ceramides in stratum comeum of atopic dermatitis: an etiologic factor in atopic dry skin. J Invest Dermatol. 1991; 96: 523–6

    PubMed  Article  CAS  Google Scholar 

  3. Paige DG, Morse-Fisher N, Harper JI. Quantification of stratum comeum ceramides and lipid envelope ceramides in the hereditary ichthyoses. Br J Dermalot. 1994; 131: 23–7

    Article  CAS  Google Scholar 

  4. Matsumoto M, Umemoto N, Sugiura H, et al. Difference in ceramide composition between “dry” and “normal” skin in patients with atopic dermatitis. Acta Derm Venereol. 1999; 79: 246–7

    PubMed  Article  CAS  Google Scholar 

  5. Pilgram GS, Vissers DC, van der Meulen H, et al. Aberrant lipid organization in stratum corneum of patients with atopic dermatitis and lamellar ichthyosis. J Invest Dermatol. 2001; 117: 710–7

    PubMed  Article  CAS  Google Scholar 

  6. Macheleidt O, Kaiser HW, Sandhoff K. Deficiency of epidermal protein-bound omega-hydroxyceramides in atopic dermatitis. J Invest Dermatol. 2002; 119: 166–73

    PubMed  Article  CAS  Google Scholar 

  7. Geilen CC, Wieder T, Orfanos CE. Ceramide signalling: regulatory role in cell proliferation, differentiation and apoptosis in human epidermis. Arch Dermatol Res. 1997; 289 (10): 559–66

    PubMed  Article  CAS  Google Scholar 

  8. Burek C, Roth J, Koch HG, et al. The role of ceramide in receptor and stress-induced apoptosis studied in acidic ceramidase-deficient Farber disease cells. Oncogene. 2001; 20: 6493–502

    PubMed  Article  CAS  Google Scholar 

  9. Komatsu M, Takahashi T, Abe T, et al. Evidence for the association of ultraviolet-C and Hb2Ob2-induced apoptosis with acid sphingomyelinase activation. Biochim Biophys Acta. 2001; 1533: 47–54

    PubMed  Article  CAS  Google Scholar 

  10. Separovic D, Mann KJ, Oleinick NL. Association of ceramide accumulation with photodynamic treatment-induced cell death. Photochem Photobiol 1998; 68: 101–9

    PubMed  Article  CAS  Google Scholar 

  11. Pena LA, Fuks Z, Kolesnick R. Stress-induced apoptosis and the sphingomyelin pathway. Biochem Pharmacol. 1997; 53: 615–21

    PubMed  Article  CAS  Google Scholar 

  12. Kolesnick R. The therapeutic potential of modulating the ceramide/sphingomyelin pathway. J Clin Invest. 2002; 110: 3–8

    PubMed  CAS  Google Scholar 

  13. Ogretmen B, Hannun YA. Updates on functions of ceramides in chemotherapy-induced cell death and in multidrug resistance. Drug Resist Updat. 2001; 4: 368–77

    PubMed  Article  CAS  Google Scholar 

  14. Claus R, Russwurm S, Meisner M, et al. Modulation of the ceramide level: a novel therapeutic concept?. Curr Drug Targets. 2000; 1: 185–205

    PubMed  Article  CAS  Google Scholar 

  15. Lucci A, Han TY, Liu YY, et al. Multidrug resistance modulators and doxorubicin synergize to elevate ceramide levels and elicit apoptosis in drug-resistant cancer cells. Cancer. 1999; 86: 300–11

    PubMed  Article  CAS  Google Scholar 

  16. Charles AG, Han TY, Liu YY, et al. Taxol-induced ceramide generation and apoptosis in human breast cancer cells. Cancer Chemother Pharmaco. 2001; 47: 444–50

    Article  CAS  Google Scholar 

  17. Holleran WM, Feingold KR, Man MQ, et al. Regulation of epidermal sphingolipid synthesis by permeability barrier function. J Lipid Res. 1991; 32 (7): 1151–8

    PubMed  CAS  Google Scholar 

  18. Holleran WM, Takagi Y, Menon GK, et al. Permeability barrier requirements regulate epidermal β-glucocerebrosidase. J Lipid Res. 1995; 35: 905–12

    Google Scholar 

  19. Jensen JM, Schiitze S, Förl M, et al. Roles for tumor necrosis factor receptor p55 and sphingomyelinase in repairing the cutaneous permeability barrier. J Clin Invest. 1999; 104: 1761–70

    PubMed  Article  CAS  Google Scholar 

  20. Higuchi K, Hara J, Okamoto R, et al. The skin of atopic dermatitis patients contains a novel enzyme, glucosylceramide sphingomyelin deacylase, which cleaves the N-acyl linkage of sphingomyelin and glucosylceramide. Biochem J. 2000; 350: 747–56

    PubMed  Article  CAS  Google Scholar 

  21. Hara J, Higuchi K, Okamoto R, et al. High-expression of sphingomyelinase deacylase is an important determinant of ceramide deficiency leading to barrier disruption atopic dermatitis. J Invest Dermatol. 2000; 115: 406–13

    PubMed  Article  CAS  Google Scholar 

  22. Ishibashi M, Arikawa J, Okamoto R, et al. Abnormal expression of the novel epidermal enzyme, glucosylceramide deacylase, and the accumulation of its enzymatic reaction product, glucosylsphingosine, in the skin of patients with atopic dermatitis. Lab Invest. 2003; 83: 397–408

    PubMed  CAS  Google Scholar 

  23. Wilkening G, Linke T, Sandhoff K. Lysosomal degradation on vesicular membrane surfaces. J Biol Chem. 1998; 273: 30271–8

    PubMed  Article  CAS  Google Scholar 

  24. Tayama M, Soeda S, Kishimoto Y, et al. Effect of saposins on acid sphingomyelinase. Biochem J. 1993; 290: 401–4

    PubMed  CAS  Google Scholar 

  25. Hammond SA, Tsonis C, Sellins K, et al. Transcutaneous immunization of domestic animals: opportunities and challenges. Adv Drug Deliv Rev. 2000; 43: 45–55

    PubMed  Article  CAS  Google Scholar 

  26. Ponec M, Weerheim A, Lankhorst P, et al. New acylceramide in native and reconstructed epidermis. J Invest Dermatol. 2003; 120: 581–8

    PubMed  Article  CAS  Google Scholar 

  27. Bouwstra JA, Gooris GS, Dubbelaar FER, et al. Phase behavior of stratum corneum lipid mixtures based on human ceramides: the role of natural and synthetic ceramide 1. J Invest Dermatol. 2002; 118: 606–17

    PubMed  Article  CAS  Google Scholar 

  28. Bouwstra JA, Gooris GS, Dubbelaar FER, et al. Phase behavior of lipid mixtures based on human ceramides: coexistence of crystalline and lipid phases. J Lipid Res. 2001; 42: 1759–70

    PubMed  CAS  Google Scholar 

  29. 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: 3725–32

    PubMed  Article  CAS  Google Scholar 

  30. Bouwstra JA, Goods GS, van der Spek JA, et al. Structural investigations of human stratum comeum by small-angle x-ray scattering. J Invest Dermatol. 1991; 97: 1005–12

    PubMed  Article  CAS  Google Scholar 

  31. Bouwstra JA, Goods GS, van der Spek JA, et al. The lipid and protein structure of mouse stratum comeum: a wide and small angle diffraction study. Biochim Biophys Acta. 1994; 1212: 183–92

    PubMed  Article  CAS  Google Scholar 

  32. Pilgram GS, Engelsma-van Pelt AM, Bouwstra JA, et al. Electron diffraction provides new information on human stratum comeum lipid organization studied in relation to death and temperature. J Invest Dermatol. 1999; 113: 403–9

    PubMed  Article  CAS  Google Scholar 

  33. Bouwstra JA, Honeywell-Nguyen PL. Skin structure and mode of vesicles. Adv Drug Deliv Rev. 2002; 54: s41–55

    PubMed  Article  CAS  Google Scholar 

  34. Jin K, Higaki Y, Tagaki Y, et al. Analysis of beta-glucocerebrosidase and ceramidase activities in atopic and aged dry skin. Acta Derm Venereol. 1994; 74: 337–40

    PubMed  CAS  Google Scholar 

  35. Imokawa G, Akasaki S, Hattori M, et al. Selective recovery of deranged water-holding properties by stratum lipids. J Invest Dermatol. 1986; 87: 758–61

    PubMed  Article  CAS  Google Scholar 

  36. Di Nardo A, Wertz P, Giannetti A, et al. Ceramide and cholesterol composition of the skin of patients with atopic dermatitis. Acta Derm Venereol. 1998; 78: 27–30

    PubMed  Article  CAS  Google Scholar 

  37. 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: 1242–9

    PubMed  Article  CAS  Google Scholar 

  38. Yamamoto A, Serizawa S, Ito M, et al. Stratum comeum lipid abnormalities in atopic dermatitis. Arch Dermatol Res. 1991; 283: 219–23

    PubMed  Article  CAS  Google Scholar 

  39. Ohnishi Y, Okino N, Ito M, et al. Ceramidase activity in bacterial skin flora as a possible cause of ceramide deficiency in atopic dermatitis. Clin Diagn Lab Immunol. 1999; 6: 101–4

    PubMed  CAS  Google Scholar 

  40. Kusuda S, Chang-Yi C, Takahashi M, et al. Localization of sphingomyelinase in lesional skin of atopic dermatitis patients. J Invest Dermatol. 1998; 111: 733–8

    PubMed  Article  CAS  Google Scholar 

  41. Chang-Yi C, Kusuda S, Seguchi T, et al. Decreased level of prosaposin in atopic skin. J Invest Dermatol. 1997; 109: 319–23

    Article  Google Scholar 

  42. Jensen JM, Folster-Holst R, Baranowsky A, et al. Impaired sphingomyelinase activity and epidermal differentiation in atopic dermatitis. J Invest Dermatol. 2004; 122 (6): 1423–31

    PubMed  Article  CAS  Google Scholar 

  43. Arikawa J, Ishibashi M, Kawashima M, et al. Decreased levels of sphingosine, a natural antimicrobial agent, may be associated with vulnerability of the stratum comeum from patients with atopic dermatitis to colonization by Staphylococcus aureus. J Invest Dermatol. 2002; 119: 433–9

    PubMed  Article  CAS  Google Scholar 

  44. Okamoto R, Arikawa J, Ishibashi M, et al. Sphingosylphosphorylcholine is upregulated in the stratum corneum of patients with atopic dermatitis. J Lipid Res. 2003; 44: 93–102

    PubMed  Article  CAS  Google Scholar 

  45. Uchida Y, Hara M, Nishio M, et al. Epidermal sphingomyelins are precursors for selected stratum comeum ceramides. J Lipid Res. 2000; 41: 2071–82

    PubMed  CAS  Google Scholar 

  46. Motta S, Monti M, Sesana S, et al. Abnormality of water barrier function in psoriasis: role of ceramide functions. Arch Dermatol. 1994; 130: 452–6

    PubMed  Article  CAS  Google Scholar 

  47. Motta S, Sesana S, Monti M, et al. Interlamellar lipid difference between normal and psoriatic stratum corneum. Acta Derm Venereol Suppl. 1994; 186: 131–2

    CAS  Google Scholar 

  48. Motta S, Monti M, Sesana S, et al. Ceramide composition of the psoriatic scale. Biochim Biophys Acta. 1993; 1182: 147–51

    PubMed  Article  CAS  Google Scholar 

  49. 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

    PubMed  Article  CAS  Google Scholar 

  50. Sidransky E, Fartasch M, Lee RE, et al. Epidermal abnormalities may distinguish type 2 from type 1 and type 3 of Gaucher disease. Pediatr Res. 1996; 39: 134–41

    PubMed  Article  CAS  Google Scholar 

  51. Holleran WM, Ginns EI, Menon GK, et al. Consequences of β-glucocerebrosidase deficiency in epidermis: ultrastructure and permeability barrier alterations in Gaucher disease. J Clin Invest. 1994; 93 (4): 1756–64

    PubMed  Article  CAS  Google Scholar 

  52. Doering T, Proia RL, Sandhoff K. Accumulation of protein-bound epidermal glucosylceramides in β-glucocerebrosidase deficient type 2 Gaucher mice. FEBS Lett. 1999; 447: 167–70

    PubMed  Article  CAS  Google Scholar 

  53. Orbisky E, Sidransky E, McKinney CE, et al. Glucosylsphingosine accumulation in mice and patients with type 2 Gaucher disease begins early in gestation. Pediatr Res. 2000; 48: 233–7

    Article  Google Scholar 

  54. Ida H, Rennert OM, Eto Y, et al. Cloning of a human acid sphingomyelinase cDNA with a new mutation that renders the enzyme inactive. J Biochem. 1993; 114: 15–20

    PubMed  CAS  Google Scholar 

  55. Schmuth M, Man MQ, Weber F, et al. Permeability barrier disorder in Niemann-Pick disease: sphingomyelin-ceramide processing required for normal barrier homeostasis. J Invest Dermatol. 2000; 115: 459–66

    PubMed  Article  CAS  Google Scholar 

  56. Muramatsu T, Sakai N, Yanagihara I, et al. Mutation analysis of the acid ceramidase gene in Japanese patients with Farber disease. J Inherit Metab Dis. 2002; 25: 585–92

    PubMed  Article  CAS  Google Scholar 

  57. De Paepe K, Roseeuw D, Rogiers V. Repair of acetone-and sodium lauryl sulfate-damaged human skin barrier function using topically applied emulsions containing barrier lipids. J Fur Acad Dermatol Venereol. 2002; 16: 587–94

    Article  CAS  Google Scholar 

  58. Coderch L, De Pera M, Fonollosa J, et al. Efficacy of stratum comeum lipid supplementation on human skin. Contact Dermatitis. 2002; 47: 139–46

    PubMed  Article  CAS  Google Scholar 

  59. Man MM, Feingold KR, Thomfeldt CR, et al. Optimization of physiological lipid mixtures for barrier repair. J Invest Dermatol. 1996; 106: 1096–101

    Article  Google Scholar 

  60. Berardesca E, Barbareschi M, Veraldi S, et al. Evaluation of efficiency of a skin lipid mixture in patients with irritant contact dermatitis, allergic contact dermatitis or atopic dermatitis: a multicenter study. Contact Dermatitis. 2001; 45: 280–5

    PubMed  Article  CAS  Google Scholar 

  61. Kucharekova M, Schalkwijk J, van de Kerkhof PCM, et al. Effect of a lipid-rich emollient containing ceramide 3 in experimentally induced skin barrier dysfunction. Contact Dermatitis. 2002; 46: 331–8

    PubMed  Article  CAS  Google Scholar 

  62. Chamlin SL, Kao J, Frieden IJ, et al. Ceramide-dominant barrier repair lipids alleviate childhood atopic dermatitis: changes in barrier function provide a sensitive indicator of disease activity. J Am Acad Dermatol. 2002; 47: 198–208

    PubMed  Article  Google Scholar 

Download references

Acknowledgments

The authors have provided no information on sources of funding or on conflicts of interest directly relevant to the content of this review.

Author information

Authors and Affiliations

  1. Department of Dermatology, School of Medicine, University of California, Surge 110, 90 Medical Center Way, Box 0989, San Francisco, California, CA 94143-0989, USA

    Myeong Jun Choi &  Howard I. Maibach

  2. Charmzone Research and Development Center, Won-Ju, Kangwon-do, Korea

    Myeong Jun Choi

Authors
  1. Myeong Jun Choi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Howard I. Maibach
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Howard I. Maibach.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Choi, M.J., Maibach, H.I. Role of Ceramides in Barrier Function of Healthy and Diseased Skin. Am J Clin Dermatol 6, 215–223 (2005). https://doi.org/10.2165/00128071-200506040-00002

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00128071-200506040-00002

Keywords

  • Atopic Dermatitis
  • Ceramide
  • Stratum Corneum
  • Gauche Disease
  • Atopic Dermatitis Patient