Impact of Stratum Corneum Damage on Natural Moisturizing Factor (NMF) in the Skin

  • Lisa M. Kroll
  • Douglas R. Hoffman
  • Corey Cunningham
  • David W. Koenig


The stratum corneum (SC) is a complex structure that protects our bodies and makes it possible for mammalian life on this planet. The SC employs a combination of both physical and biochemical processes to limit the movement of water in and out of the body although clearly it is the latter that is of most importance. The SC can be disturbed by comparatively minor injury caused by mechanical, occlusive, enzymatic, and chemical damages. Lipids and a family of hygroscopic molecules known as natural moisturizing factor (NMF) are vital to the SC’s ability to regulate epidermal permeability. This chapter reviews what is known about the impact of barrier disruption on key skin components and provides new insights into NMF responses following damage induced by sodium lauryl sulfate (SLS).


Stratum Corneum Sodium Lauryl Sulfate Lamellar Body Arginase Activity Barrier Disruption 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. 1.
    Motta S, Monti M, Sesana S, Caputo R, Carelli S, Ghidoni R (1993) Ceramide composition of the psoriatic scale. Biochim Biophys Acta 1182(2):147–151PubMedGoogle Scholar
  2. 2.
    Cookson WO, Ubhi B, Lawrence R, Abecasis GR, Walley AJ, Cox HE, Coleman R, Leaves NI, Trembath RC, Moffatt MF, Harper JI (2001) Genetic linkage of childhood atopic dermatitis to psoriasis susceptibility loci. Nat Genet 27(4):372–373PubMedCrossRefGoogle Scholar
  3. 3.
    Sator PG, Schmidt JB, Hönigsmann H (2003) Comparison of epidermal hydration and skin surface lipids in health individuals and in patients with atopic dermatitis. J Am Acad Dermatol 48(3):352–358PubMedCrossRefGoogle Scholar
  4. 4.
    Proksch E, Elias PM (2002) Epidermal barrier in atopic dermatitis. In: Beiber T, Leung DY (eds) Atopic dermatitis. Marcel Dekker, New YorkGoogle Scholar
  5. 5.
    Schulze C, Wetzel F, Kueper T, Malsen A, Muhr G, Jaspers S, Blatt T, Wittern KP, Wenck H, Käs JA (2010) Stiffening of human skin fibroblasts with age. Biophys J 99(8):2434–2442PubMedCrossRefGoogle Scholar
  6. 6.
    Fluhr JW, Akengin A, Bornkessel A, Fuchs S, Praessler J, Norgauer J, Grieshaber R, Kleesz P, Elsner P (2005) Additive impairment of the barrier function by mechanical irritation, occlusion, and sodium lauryl sulphate in vivo. Br J Dermatol 153(1):125–131PubMedCrossRefGoogle Scholar
  7. 7.
    Shindo Y, Witt E, Han D, Packer L (1994) Dose–response effects of acute ultraviolet irradiation on antioxidants and molecular markers of oxidation in murine epidermis and dermis. J Invest Dermatol 102(4):470–475PubMedCrossRefGoogle Scholar
  8. 8.
    Shindo Y, Witt E, Packer L (1993) Antioxidant defense mechanisms in murine epidermis and dermis and their responses to ultraviolet light. J Invest Dermatol 100(3):260–265PubMedCrossRefGoogle Scholar
  9. 9.
    Thiele JJ, Traber MG, Packer L (1998) Depletion of human stratum corneum vitamin E: an early and sensitive in vivo marker of UV-induced photooxidation. J Invest Dermatol 110(5):756–761PubMedCrossRefGoogle Scholar
  10. 10.
    Andersen PH, Bucher AP, Saeed I, Lee PC, Davis JA, Maibach HI (1994) Faecal enzymes: in vivo skin irritation. Contact Dermatitis 30(3):152–158PubMedCrossRefGoogle Scholar
  11. 11.
    Törmä H, Berne B (2009) Sodium lauryl sulphate alters mRNA expression of lipid-metabolizing enzymes and PPAR signaling in normal human skin in vivo. Exp Dermatol 18(12):1010–1015PubMedCrossRefGoogle Scholar
  12. 12.
    Moore PN, Shiloach A, Puvvada S, Blankschtein D (2003) Penetration of mixed micelles into the epidermis: effect of mixing sodium dodecyl sulfate with dodecyl hexa (ethylene oxide). J Cosmet Sci 54(2):143–159PubMedGoogle Scholar
  13. 13.
    Fartasch M (1997) Ultrastructure of the epidermal barrier after irritation. Microsc Res Tech 37(3):193–199PubMedCrossRefGoogle Scholar
  14. 14.
    Feingold KR (1991) The regulation of epidermal lipid synthesis by permeability barrier requirements. Crit Rev Ther Drug Carrier Syst 8(3):193–210PubMedGoogle Scholar
  15. 15.
    Grubauer G, Feingold KR, Harris RM, Elias PM (1989) Lipid content and lipid type as determinants of the epidermal permeability barrier. J Lipid Res 30(1):89–96PubMedGoogle Scholar
  16. 16.
    Harris IR, Farrell AM, Grunfeld C, Holleran WM, Elias PM, Feingold KR (1997) Permeability barrier disruption coordinately regulates mRNA levels for key enzymes of cholesterol, fatty acid, and ceramide synthesis in the epidermis. J Invest Dermatol 109(6):783–787PubMedCrossRefGoogle Scholar
  17. 17.
    Holleran WM, Takagi Y, Menon GK, Jackson SM, Lee JM, Feingold KR, Elias PM (1994) Permeability barrier requirements regulate epidermal β-glucocerebrosidase. J Lipid Res 35(5):905–912PubMedGoogle Scholar
  18. 18.
    Lasch J, Schönfelder U, Walke M, Zellmer S, Beckert D (1997) Oxidative damage of human skin lipids. Dependence of lipid peroxidation on sterol concentration. Biochim Biophys Acta 1349(2):171–181PubMedGoogle Scholar
  19. 19.
    Mao-Qiang M, Elias PM, Feingold KR (1993) Fatty acids are required for epidermal permeability barrier function. J Clin Invest 92(2):791–798PubMedCrossRefGoogle Scholar
  20. 20.
    Mao-Qiang M, Feingold KR, Jain M, Elias PM (1995) Extracellular processing of phospholipids is required for permeability barrier homeostasis. J Lipid Res 36(9):1925–1935PubMedGoogle Scholar
  21. 21.
    Proksch E, Holleran WM, Menon GK, Elias PM, Feingold KR (1993) Barrier function regulates epidermal lipid and DNA synthesis. Br J Dermatol 128(5):473–482PubMedCrossRefGoogle Scholar
  22. 22.
    Takagi Y, Kriehuber E, Imokawa G, Elias PM, Holleran WM (1999) β-Glucocerebrosidase activity in mammalian stratum corneum. J Lipid Res 40(5):861–869PubMedGoogle Scholar
  23. 23.
    Choi EH, Man MQ, Xu P, Xin S, Liu Z, Crumrine DA, Jiang YJ, Fluhr JW, Feingold KR, Elias PM, Mauro TM (1991) Stratum corneum acidification is impaired in moderately aged human and murine skin. J Invest Dermatol 127(12):2847–2856CrossRefGoogle Scholar
  24. 24.
    Denda M, Tsutsumi M, Inoue K, Crumrine D, Feingold KR, Elias PM (2007) Potassium channel openers accelerate epidermal barrier recovery. Br J Dermatol 157(5):888–893PubMedCrossRefGoogle Scholar
  25. 25.
    Elias PM, Ahn SK, Denda M, Brown BE, Crumrine D, Kimutai LK, Kömüves L, Lee SH, Feingold KR (2002) Modulations in epidermal calcium regulate the expression of differentiation-specific markers. J Invest Dermatol 119(5):1128–1136PubMedCrossRefGoogle Scholar
  26. 26.
    Mauro T, Holleran WM, Grayson S, Gao WN, Man MQ, Kriehuber E, Behne M, Feingold KR, Elias PM (1998) Barrier recovery is impeded at neutral pH, independent of ionic effects: implications for extracellular lipid processing. Arch Dermatol Res 290(4):215–222PubMedCrossRefGoogle Scholar
  27. 27.
    Rawlings AV, Scott IR, Harding CR, Bowser PA (1994) Stratum corneum moisturization at the molecular level. J Invest Dermatol 103(5):731–741PubMedCrossRefGoogle Scholar
  28. 28.
    Sandilands A, Sutherland C, Irvine AD, McLean WH (2009) Filaggrin in the frontline: role in skin barrier function and disease. J Cell Sci 122(Pt 9):12851294Google Scholar
  29. 29.
    McGrath JA, Uitto J (2008) The filaggrin story: novel insights into skin-barrier function and disease. Trends Mol Med 14(1):20–27PubMedCrossRefGoogle Scholar
  30. 30.
    Palmer CN, Irvine AD, Terron-Kwiatkowski A, Zhao Y, Liao H, Lee SP, Goudie DR, Sandilands A, Campbell LE, Smith FJ, O’Regan GM, Watson RM, Cecil JE, Bale SJ, Compton JG, DiGiovanna JJ, Fleckman P, Lewis-Jones S, Arseculeratne G, Sergeant A, Munro CS, El Houate B, McElreavey K, Halkjaer LB, Bisgaard H, Mukhopadhyay S, McLean WH (2006) Common loss-of-function variants of the epidermal barrier protein filaggrin are a major predisposing factor for atopic dermatitis. Nat Genet 38(4):441–446PubMedCrossRefGoogle Scholar
  31. 31.
    Rawlings AV (2006) Sources and role of stratum corneum hydration. In: Elias PM, Feingold KR (eds) Skin barrier. Taylor & Francis, New YorkGoogle Scholar
  32. 32.
    Harding CR, Watkinson A, Rawlings AV, Scott IR (2000) Dry skin, moisturization and corneodesmolysis. Int J Cosmet Sci 22(1):21–52PubMedCrossRefGoogle Scholar
  33. 33.
    Nakagawa N, Sakai S, Matsumoto M, Yamada K, Nagano M, Yuki T, Sumida Y, Uchiwa H (2004) Relationship between NMF (lactate and potassium) content and the physical properties of the stratum corneum in healthy subjects. J Invest Dermatol 122(3):755–763PubMedCrossRefGoogle Scholar
  34. 34.
    Koyama J, Horii I, Kawasaki K (1984) Free amino acids of stratum corneum as a biochemical marker to evaluate dry skin. J Cosmet Chem Japan 35(4):183–195Google Scholar
  35. 35.
    Kroll LM, Hoffman DR, Basehoar A, Cunningham C, Reece B, Koenig DW (2011) Confocal Raman study of stratum corneum changes after damage with sodium lauryl sulfate. In: International Society for Biophysics and Imaging of the Skin (ISBS). US technical symposium of ISBS, Tampa Bay, 6–9 Apr 2011Google Scholar
  36. 36.
    Porcheron A, Mauger E, Guinot C, Tschachler E, Morizot F (2007) Abstracts from the stratum corneum V conference 2007. Int J Cosmet Sci 29(3):219–228CrossRefGoogle Scholar
  37. 37.
    Pratzel H, Fries P (1977) Modification of relative amount of free amino acids in the stratum corneum of human epidermis by special factors of the environment. I. The influence of UV irradiation. Arch Dermatol Res 259(2):157–160PubMedCrossRefGoogle Scholar
  38. 38.
    Scott IR (1986) Alterations in the metabolism of filaggrin in the skin after chemical- and ultraviolet-induced erythema. J Invest Dermatol 87(4):460–465PubMedCrossRefGoogle Scholar
  39. 39.
    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 128:1212–1219PubMedCrossRefGoogle Scholar
  40. 40.
    Visscher M, Robinson M, Wickett R (2011) Stratum corneum free amino acids following barrier perturbation and repair. Int J Cosmet Sci 33(1):80–89PubMedCrossRefGoogle Scholar
  41. 41.
    Presland RB, Rothnagel JA, Lawrence OT (2006) Profilaggrin and the fused S100 family of calcium-binding proteins. In: Elias PM, Feingold KR (eds) Skin barrier. Taylor & Francis, New YorkGoogle Scholar
  42. 42.
    Presland RB, Kimball JR, Kautsky MB, Lewis SP, Lo CY, Dale BA (1997) Evidence for specific proteolytic cleavage of the N-terminal domain of the human profilaggrin during epidermal differentiation. J Invest Dermatol 108(2):170–178PubMedCrossRefGoogle Scholar
  43. 43.
    Pearton DJ, Nirunsuksiri W, Rehemtulla A, Lewis SP, Presland RB, Dale BA (2001) Proprotein convertase expression and localization in epidermis: evidence for multiple roles and substrates. Exp Dermatol 10(3):193–203PubMedCrossRefGoogle Scholar
  44. 44.
    Resing KA, Walsh KA, Haugen-Scofield J, Dale BA (1989) Identification of proteolytic cleavage sites in the conversion of profilaggrin to filaggrin in mammalian epidermis. J Biol Chem 264(3):1837–1845PubMedGoogle Scholar
  45. 45.
    Resing KA, al-Alawi N, Blomquist C, Fleckman P, Dale BA (1993) Independent regulation of two cytoplasmic processing stages of the intermediate filament-associated protein filaggrin and role of Ca2+ in the second stage. J Biol Chem 268(33):25139–25145PubMedGoogle Scholar
  46. 46.
    Resing KA, Thulin C, Whiting K, al-Alawi N, Mostad S (1995) Characterization of profilaggrin endoproteinase 1. A regulated cytoplasmic endoproteinase of epidermis. J Biol Chem 270(47):28193–28198PubMedCrossRefGoogle Scholar
  47. 47.
    Yamazaki M, Ishidoh K, Suga Y, Saido TC, Kawashima S, Suzuki K, Kominami E, Ogawa H (1997) Cytoplasmic processing of human profilaggrin by active mu-calpain. Biochem Biophys Res Commun 235(3):652–656PubMedCrossRefGoogle Scholar
  48. 48.
    Tarcsa E, Marekov LN, Mei G, Melino G, Lee SC, Steinert PM (1996) Protein unfolding by peptidylarginine deiminase. Substrate specificity and structural relationships of the natural substrates trichohyalin and filaggrin. J Biol Chem 271(48):30709–30716PubMedCrossRefGoogle Scholar
  49. 49.
    Vossenaar ER, Zendman AJ, van Venrooij WJ, Pruijn GJ (2003) PAD, a growing family of citrullinating enzymes: genes, features and involvement in disease. Bioessays 25(11):1106–1118PubMedCrossRefGoogle Scholar
  50. 50.
    Chavanas S, Méchin MC, Nachat R, Adoue V, Coudane F, Serre G, Simon M (2006) Peptidylarginine deiminases and deimination in biology and pathology: relevance to skin homeostasis. J Dermatol Sci 44(2):63–72PubMedCrossRefGoogle Scholar
  51. 51.
    Elias PM (2004) The epidermal permeability barrier: from the early days at Harvard to emerging concepts. J Invest Dermatol 122(2):xxxvi–xxxixPubMedCrossRefGoogle Scholar
  52. 52.
    Kawada A, Hara K, Hiruma M, Noguchi H, Ishibashi A (1995) Rat epidermal cathepsin L-like proteinase: purification and some hydrolytic properties toward filaggrin and synthetic substrates. J Biochem 118(2):332–337PubMedGoogle Scholar
  53. 53.
    Kawada A, Hara K, Morimoto K, Hiruma M, Ishibashi A (1995) Rat epidermal cathepsin B: purification and characterization of proteolytic properties toward filaggrin and synthetic substrates. Int J Biochem Cell Biol 27(2):175–183PubMedCrossRefGoogle Scholar
  54. 54.
    Benavides F, Starost MF, Flores M, Gimenez-Conti IB, Guénet JL, Conti CJ (2002) Impaired hair follicle morphogenesis and cycling with abnormal epidermal differentiation in nackt mice, a cathepsin L-deficient mutation. Am J Pathol 161(2):693–703PubMedCrossRefGoogle Scholar
  55. 55.
    Tabachnick J, LaBadie JH (1970) Studies on the biochemistry of epidermis. IV. The free amino acids, ammonia, urea, and pyrrolidone carboxylic acid content of conventional and germ-free albino guinea pig epidermis. J Invest Dermatol 54(1):24–31PubMedCrossRefGoogle Scholar
  56. 56.
    Kamata Y, Taniguchi A, Yamamoto M, Nomura J, Ishihara K, Takahara H, Hibino T, Takeda A (2009) Neutral cysteine protease bleomycin hydrolase is essential for the breakdown of deiminated filaggrin into amino acids. J Biol Chem 284(19):12829–12836PubMedCrossRefGoogle Scholar
  57. 57.
    Gibson WT, Teall MR (1983) Interactions of C12 surfactants with the skin: changes in enzymes and visible and histological features of rat skin treated with sodium lauryl sulphate. Food Chem Toxicol 21(5):587–594PubMedCrossRefGoogle Scholar
  58. 58.
    Le M, Schalkwijk J, Siegenthaler G, Van De Kerkhof PCM, Veerkamp JH, Van Der Valk PGM (1996) Changes in keratinocyte differentiation following mild irritation by sodium dodecyl sulfate. Arch Dermatol Res 288(11):684–690PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2012

Authors and Affiliations

  • Lisa M. Kroll
    • 1
  • Douglas R. Hoffman
    • 1
  • Corey Cunningham
    • 1
  • David W. Koenig
    • 1
  1. 1.Corporate Research & EngineeringKimberly-Clark CorporationNeenahUSA

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