Skip to main content
NCBI home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1994 Jul;94(1):89–96. doi: 10.1172/JCI117352

Pseudo-acylceramide with linoleic acid produces selective recovery of diminished cutaneous barrier function in essential fatty acid-deficient rats and has an inhibitory effect on epidermal hyperplasia.

G Imokawa 1, Y Yada 1, K Higuchi 1, M Okuda 1, Y Ohashi 1, A Kawamata 1
PMCID: PMC296285  PMID: 8040295

Abstract

Pseudo-acylceramides with different acyl properties were investigated for their capacity to restore diminished barrier function in essential fatty acid-deficient rats. Daily topical applications of synthetic pseudo-acylceramides containing ester-linked linoleic acid caused a dose-dependent, significant reduction of transepidermal water loss (TEWL). Both other pseudo-acylceramides with ester-linked oleic acid or saturated alkyl chains and ordinary ceramides exhibited a poor effect on recovery of TEWL. Furthermore, pseudoceramide containing ether-linked linoleic acid, which is biologically inactive in terms of degradation by hydrolytic enzymes, also induced a significant and similar increase in the barrier function. This restoration of barrier function by pseudo-acylceramides with linoleic acid was accompanied by suppressed DNA synthesis in the EFAD rat epidermis. In UVB-irradiated guinea pig skin, topical applications of the pseudo-acylceramides with linoleic acid immediately after the exposure significantly reduced epidermal hyperplasia, secondary to markedly diminished barrier disruption, whereas linoleic acid itself did not. A comparison of both the anti-hyperplasia and the barrier recovery effects in the series of pseudo-ceramide derivatives examined revealed that the suppressive effect on the induced epidermal hyperplasia was paralleled by the recovery of the barrier defect in EFAD rats. These findings directly suggest that acylceramide with an ester-linked linoleic acid has an essential role in the epidermal permeability barrier.

Full text

PDF
89

Images in this article

92Image
on p.92
93Image
on p.93
94Image
on p.94

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bowser P. A., Nugteren D. H., White R. J., Houtsmuller U. M., Prottey C. Identification, isolation and characterization of epidermal lipids containing linoleic acid. Biochim Biophys Acta. 1985 May 17;834(3):419–428. doi: 10.1016/0005-2760(85)90016-5. [DOI] [PubMed] [Google Scholar]
  2. Elias P. M., Brown B. E., Ziboh V. A. The permeability barrier in essential fatty acid deficiency: evidence for a direct role for linoleic acid in barrier function. J Invest Dermatol. 1980 Apr;74(4):230–233. doi: 10.1111/1523-1747.ep12541775. [DOI] [PubMed] [Google Scholar]
  3. Elias P. M., Friend D. S. The permeability barrier in mammalian epidermis. J Cell Biol. 1975 Apr;65(1):180–191. doi: 10.1083/jcb.65.1.180. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Elliott W. J., Morrison A. R., Sprecher H. W., Needleman P. The metabolic transformations of columbinic acid and the effect of topical application of the major metabolites on rat skin. J Biol Chem. 1985 Jan 25;260(2):987–992. [PubMed] [Google Scholar]
  5. Elliott W. J., Sprecher H., Needleman P. Physiologic effects of columbinic acid and its metabolites on rat skin. Biochim Biophys Acta. 1985 Jun 14;835(1):158–160. doi: 10.1016/0005-2760(85)90043-8. [DOI] [PubMed] [Google Scholar]
  6. Feingold K. R., Man M. Q., Proksch E., Menon G. K., Brown B. E., Elias P. M. The lovastatin-treated rodent: a new model of barrier disruption and epidermal hyperplasia. J Invest Dermatol. 1991 Feb;96(2):201–209. doi: 10.1111/1523-1747.ep12461153. [DOI] [PubMed] [Google Scholar]
  7. Grubauer G., Elias P. M., Feingold K. R. Transepidermal water loss: the signal for recovery of barrier structure and function. J Lipid Res. 1989 Mar;30(3):323–333. [PubMed] [Google Scholar]
  8. Grubauer G., Feingold K. R., Harris R. M., Elias P. M. Lipid content and lipid type as determinants of the epidermal permeability barrier. J Lipid Res. 1989 Jan;30(1):89–96. [PubMed] [Google Scholar]
  9. Imokawa G., Akasaki S., Hattori M., Yoshizuka N. Selective recovery of deranged water-holding properties by stratum corneum lipids. J Invest Dermatol. 1986 Dec;87(6):758–761. doi: 10.1111/1523-1747.ep12456950. [DOI] [PubMed] [Google Scholar]
  10. Imokawa G., Akasaki S., Minematsu Y., Kawai M. 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(1):45–51. doi: 10.1007/BF00424272. [DOI] [PubMed] [Google Scholar]
  11. Imokawa G., Hattori M. A possible function of structural lipids in the water-holding properties of the stratum corneum. J Invest Dermatol. 1985 Apr;84(4):282–284. doi: 10.1111/1523-1747.ep12265365. [DOI] [PubMed] [Google Scholar]
  12. Imokawa G., Kuno H., Kawai M. Stratum corneum lipids serve as a bound-water modulator. J Invest Dermatol. 1991 Jun;96(6):845–851. doi: 10.1111/1523-1747.ep12474562. [DOI] [PubMed] [Google Scholar]
  13. Imokawa G., Tejima T. A possible role of prostaglandins in PUVA-induced inflammation: implication by organ cultured skin. J Invest Dermatol. 1989 Feb;92(2):296–300. doi: 10.1111/1523-1747.ep12276882. [DOI] [PubMed] [Google Scholar]
  14. Lampe M. A., Burlingame A. L., Whitney J., Williams M. L., Brown B. E., Roitman E., Elias P. M. Human stratum corneum lipids: characterization and regional variations. J Lipid Res. 1983 Feb;24(2):120–130. [PubMed] [Google Scholar]
  15. Lowe N. J., Stoughton R. B. Essential fatty acid deficient hairless mouse: a model of chronic epidermal hyperproliferation. Br J Dermatol. 1977 Feb;96(2):155–162. doi: 10.1111/j.1365-2133.1977.tb12537.x. [DOI] [PubMed] [Google Scholar]
  16. Melton J. L., Wertz P. W., Swartzendruber D. C., Downing D. T. Effects of essential fatty acid deficiency on epidermal O-acylsphingolipids and transepidermal water loss in young pigs. Biochim Biophys Acta. 1987 Sep 25;921(2):191–197. doi: 10.1016/0005-2760(87)90018-x. [DOI] [PubMed] [Google Scholar]
  17. Nugteren D. H., Christ-Hazelhof E., van der Beek A., Houtsmuller U. M. Metabolism of linoleic acid and other essential fatty acids in the epidermis of the rat. Biochim Biophys Acta. 1985 May 17;834(3):429–436. doi: 10.1016/0005-2760(85)90017-7. [DOI] [PubMed] [Google Scholar]
  18. Proksch E., Feingold K. R., Man M. Q., Elias P. M. Barrier function regulates epidermal DNA synthesis. J Clin Invest. 1991 May;87(5):1668–1673. doi: 10.1172/JCI115183. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Wertz P. W., Cho E. S., Downing D. T. Effect of essential fatty acid deficiency on the epidermal sphingolipids of the rat. Biochim Biophys Acta. 1983 Oct 11;753(3):350–355. doi: 10.1016/0005-2760(83)90058-9. [DOI] [PubMed] [Google Scholar]
  20. Wertz P. W., Downing D. T. Ceramides of pig epidermis: structure determination. J Lipid Res. 1983 Jun;24(6):759–765. [PubMed] [Google Scholar]
  21. Wood L. C., Jackson S. M., Elias P. M., Grunfeld C., Feingold K. R. Cutaneous barrier perturbation stimulates cytokine production in the epidermis of mice. J Clin Invest. 1992 Aug;90(2):482–487. doi: 10.1172/JCI115884. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES