Skip to main content

Advertisement

SpringerLink
Log in

A synthetic C16 omega-hydroxyphytoceramide improves skin barrier functions from diversely perturbed epidermal conditions

  • Original Paper
  • Published:
Archives of Dermatological Research Aims and scope Submit manuscript

Abstract

Omega-hydroxyceramides (ω-OH-Cer) play a crucial role in maintaining the integrity of skin barrier. ω-OH-Cer are the primary lipid constituents of the corneocyte lipid envelope (CLE) covalently attached to the outer surface of the cornified envelope linked to involucrin to become bound form lipids in stratum corneum (SC). CLE becomes a hydrophobic impermeable layer of matured corneocyte preventing loss of natural moisturizing factor inside the corneocytes. More importantly, CLE may also play an important role in the formation of proper orientation of intercellular lipid lamellar structure by interdigitating with the intercellular lipids in a comb-like fashion. Abnormal barrier conditions associated with atopic dermatitis but also UVB-irradiated skins are known to have lowered level of bound lipids, especially ω-OH-Cer, which indicate that ω-OH-Cer play an important role in maintaining the integrity of skin barrier. In this study, protective effects of a novel synthetic C16 omega-hydroxyphytoceramides (ω-OH-phytoceramide) on skin barrier function were investigated. Epidermal barrier disruption was induced by UVB irradiation, tape-stripping in hairless mouse and human skin. Protective effect of damaged epidermis was evaluated using the measurement of transepidermal water loss and cohesion of SC. Increased keratinocyte differentiation was verified using cultured keratinocyte through western blot. Results clearly demonstrated that a synthetic C16 ω-OH-phytoceramide enhanced the integrity of SC and accelerated the recovery of damaged skin barrier function by stimulating differentiation process. In a conclusion, a synthetic C16 ω-OH-phytoceramide treatment improved epidermal homeostasis in several disrupted conditions.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

References

  1. Behne M, Uchida Y, Seki T, Elias PM, Holleran WM (1998) Direct evidence that omega-hydroxy ceramides are important for epidermal barrier function. J Dermatol Sci 16(Supplement 1):S34

    Article  Google Scholar 

  2. Behne M, Uchida Y, Seki T, de Montellano PO, Elias PM, Holleran WM (2000) Omega-hydroxyceramides are required for corneocyte lipid envelope (CLE) formation and normal epidermal permeability barrier function. J Invest Dermatol 114(1):185–192

    Article  CAS  PubMed  Google Scholar 

  3. Berthaud F, Boncheva M (2011) Correlation between the properties of the lipid matrix and the degrees of integrity and cohesion in healthy human stratum corneum. Exp Dermatol 20(3):255–262

    Article  CAS  PubMed  Google Scholar 

  4. Candi E, Schmidt R, Melino G (2005) The cornified envelope: a model of cell death in the skin. Nat Rev Mol Cell Biol 6(4):328–340

    Article  CAS  PubMed  Google Scholar 

  5. Chakraborty AK, Funasaka Y, Pawelek JM, Nagahama M, Ito A, Ichihashi M (1999) Enhanced expression of melanocortin-1 receptor (MC1-R) in normal human keratinocytes during differentiation: evidence for increased expression of POMC peptides near suprabasal layer of epidermis. J Invest Dermatol 112(6):853–860

    Article  CAS  PubMed  Google Scholar 

  6. Chamlin SL, Kao J, Frieden IJ, Sheu MY, Fowler AJ, Fluhr JW, Williams ML, Elias PM (2002) Ceramide-dominant barrier repair lipids alleviate childhood atopic dermatitis: changes in barrier function provide a sensitive indicator of disease activity. J Am Acad Dermatol 47(2):198–208

    Article  PubMed  Google Scholar 

  7. D’Orazio J, Jarrett S, Amaro-Ortiz A, Scott T (2013) UV Radiation and the skin. Int J Mol Sci 14(6):12222–12248

    Article  PubMed  PubMed Central  Google Scholar 

  8. Eckl KM, Tidhar R, Thiele H, Oji V, Hausser I, Brodesser S, Preil ML, Onal-Akan A, Stock F, Müller D, Becker K, Casper R, Nürnberg G, Altmüller J, Nürnberg P, Traupe H, Futerman AH, Hennies HC (2013) Impaired epidermal ceramide synthesis causes autosomal recessive congenital ichthyosis and reveals the importance of ceramide acyl chain length. J Invest Dermatol 133(9):2202–2211

    Article  CAS  PubMed  Google Scholar 

  9. Elias PM (1983) Epidermal lipids, barrier function, and desquamation. J Invest Dermatol 80(1 Suppl):44s–49s

    Article  CAS  Google Scholar 

  10. Elias PM, Gruber R, Crumrine D, Menon G, Williams ML, Wakefield JS, Holleran WM, Uchida Y (2014) Formation and functions of the corneocyte lipid envelope (CLE). Biochim Biophys Acta 1841(3):314–318

    Article  CAS  PubMed  Google Scholar 

  11. Hong SP, Kim MJ, Jung MY, Jeon H, Goo J, Ahn SK, Lee SH, Elias PM, Choi EH (2008) Biopositive effects of low-dose UVB on epidermis: coordinate upregulation of antimicrobial peptides and permeability barrier reinforcement. J Invest Dermatol 128(12):2880–2887

    Article  CAS  PubMed  Google Scholar 

  12. Johnson JL, Koetsier JL, Sirico A, Agidi AT, Antonini D, Missero C, Green KJ (2014) The desmosomal protein desmoglein 1 aids recovery of epidermal differentiation after acute UV light exposure. J Invest Dermatol 134(8):2154–2162

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Jonca N, Leclerc EA, Caubet C, Simon M, Guerrin M, Serre G (2011) Corneodesmosomes and corneodesmosin: from the stratum corneum cohesion to the pathophysiology of genodermatoses. Eur J Dermatol 21(Suppl 2):35–42

    CAS  PubMed  Google Scholar 

  14. Khazanov E, Priev A, Shillemans JP, Barenholz Y (2008) Physicochemical and biological characterization of ceramide-containing liposomes: paving the way to ceramide therapeutic application. Langmuir 24(13):6965–6980

    Article  CAS  PubMed  Google Scholar 

  15. Macheleidt O, Kaiser HW, Sandhoff K (2002) Deficiency of epidermal protein-bound omega-hydroxyceramides in atopic dermatitis. J Invest Dermatol 119(1):166–173

    Article  CAS  PubMed  Google Scholar 

  16. Meguro S, Arai Y, Masukawa Y, Uie K, Tokimitsu I (2000) Relationship between covalently bound ceramides and transepidermal water loss (TEWL). Arch Dermatol Res 292(9):463–468

    Article  CAS  PubMed  Google Scholar 

  17. Rabionet M, Gorgas K, Sandhoff R (2014) Ceramide synthesis in the epidermis. Biochim Biophys Acta 1841(3):422–434

    Article  CAS  PubMed  Google Scholar 

  18. Skolová B, Janůšová B, Zbytovská J, Gooris G, Bouwstra J, Slepička P, Berka P, Roh J, Palát K, Hrabálek A, Vávrová K (2013) Ceramides in the skin lipid membranes: length matters. Langmuir 29(50):15624–15633

    Article  PubMed  Google Scholar 

  19. Swartzendruber DC, Wertz PW, Madison KC, Downing DT (1987) Evidence that the corneocyte has a chemically bound lipid envelope. J Invest Dermatol 88(6):709–713

    Article  CAS  PubMed  Google Scholar 

  20. Takagi Y, Nakagawa H, Kondo H, Takema Y, Imokawa G (2004) Decreased levels of covalently bound ceramide are associated with ultraviolet B-induced perturbation of the skin barrier. J Invest Dermatol 123(6):1102–1109

    Article  CAS  PubMed  Google Scholar 

  21. Törmä H, Lindberg M, Berne B (2008) Skin barrier disruption by sodium lauryl sulfate-exposure alters the expressions of involucrin, transglutaminase 1, profilaggrin, and kallikreins during the repair phase in human skin in vivo. J Invest Dermatol 128(5):1212–1219

    Article  PubMed  Google Scholar 

  22. Uchida Y (2014) Ceramide signaling in mammalian epidermis. Biochim Biophys Acta 1841(3):453–462

    Article  CAS  PubMed  Google Scholar 

  23. van Smeden J, Janssens M, Gooris GS, Bouwstra JA (2014) The important role of stratum corneum lipids for the cutaneous barrier function. Biochim Biophys Acta 1841(3):295–313

    Article  PubMed  Google Scholar 

  24. Wertz PW, Downing DT (1986) Covalent attachment of omega-hydroxyacid derivatives to epidermal macromolecules: a preliminary characterization. Biochem Biophys Res Commun 137(3):992–997

    Article  CAS  PubMed  Google Scholar 

  25. Wertz PW, Madison KC, Downing DT (1989) Covalently bound lipids of human stratum corneum. J Invest Dermatol 92(1):109–111

    Article  CAS  PubMed  Google Scholar 

  26. Wertz PW, Swartzendruber DC, Kitko DJ, Madison KC, Downing DT (1989) The role of the corneocyte lipid envelopes in cohesion of the stratum corneum. J Invest Dermatol 93(1):169–172

    Article  CAS  PubMed  Google Scholar 

  27. Yang L, Mao-Qiang M, Taljebini M, Elias PM, Feingold KR (1995) Topical stratum corneum lipids accelerate barrier repair after tape stripping, solvent treatment and some but not all types of detergent treatment. Br J Dermatol 133(5):679–685

    Article  CAS  PubMed  Google Scholar 

  28. Yoshida N, Sawada E, Imokawa G (2012) A reconstructed human epidermal keratinization culture model to characterize ceramide metabolism in the stratum corneum. Arch Dermatol Res 304(7):563–577

    Article  CAS  PubMed  Google Scholar 

  29. Zheng Y, Yin H, Boeglin WE, Elias PM, Crumrine D, Beier DR, Brash AR (2011) Lipoxygenases mediate the effect of essential fatty acid in skin barrier formation: a proposed role in releasing omega-hydroxyceramide for construction of the corneocyte lipid envelope. J Biol Chem 286(27):24046–24056

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Zolnik BS, Stern ST, Kaiser JM, Heakal Y, Clogston JD, Kester M, McNeil SE (2008) Rapid distribution of liposomal short-chain ceramide in vitro and in vivo. Drug Metab Dispos 36(8):1709–1715

    Article  CAS  PubMed  Google Scholar 

  31. Zuo Y, Zhuang DZ, Han R, Isaac G, Tobin JJ, McKee M, Welti R, Brissette JL, Fitzgerald ML, Freeman MW (2008) ABCA12 maintains the epidermal lipid permeability barrier by facilitating formation of ceramide linoleic esters. J Biol Chem 283(52):36624–36635

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgments

This study was supported by the National Coordinating Center for Global Cosmetics R&D (NCR) (Grant number: HN10C0000).

Author information

Authors and Affiliations

  1. Department of Chemical and Biochemical Engineering, Dongguk University, 3-26, Pil-dong, Chung-gu, Seoul, 100-715, Republic of Korea

    Myoung Jin Oh, Jin Ju Nam & Chang Seo Park

  2. LCS Biotech, Seodun-dong 103-2, Gwonseon-gu, Suwon-si, Gyeonggi-do, 441-857, Republic of Korea

    Eun Ok Lee & Jin Wook Kim

Authors
  1. Myoung Jin Oh
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jin Ju Nam
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Eun Ok Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jin Wook Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Chang Seo Park
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Chang Seo Park.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving animals were in accordance with the ethical standards of the institutional guidelines for the care and use of animals were followed (approved from Dongguk University, IACUC-2015-053). All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards (approved from Dongguk University, DUIRB-20150824-006).

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Oh, M.J., Nam, J.J., Lee, E.O. et al. A synthetic C16 omega-hydroxyphytoceramide improves skin barrier functions from diversely perturbed epidermal conditions. Arch Dermatol Res 308, 563–574 (2016). https://doi.org/10.1007/s00403-016-1674-3

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00403-016-1674-3

Keywords

Search

Navigation