The skin barrier as an innate immune element

Aberg K, Man M-Q, Gallo RL, Ganz T, Crumrine D, Brown BE, Choi E-H, Kim D-K, Feingold KR, Elias PM (2007) Co-regulation and interdependence of the epidermal permeability and antimicrobial barriers. Clin Invest J (submitted)

Aberg K, Radek K, Gallo RL, Mauro TM, Feingold KR, Elias PM (2007) Psychological stress down-regulates epidermal antimicrobial peptide expression and increases severity of cutaneous infections. J Clin Invest (in press)

Aly R, Shirley C, Cunico B, Maibach HI (1978) Effect of prolonged occlusion on the microbial flora, pH, carbon dioxide and transepidermal water loss on human skin. J Invest Dermatol 71:378–381

Arikawa J, Ishibashi M, Kawashima M, Takagi Y, Ichikawa Y, Imokawa G (2002) Decreased levels of sphingosine, a natural antimicrobial agent, may be associated with vulnerability of the stratum corneum from patients with atopic dermatitis to colonization by Staphylococcus aureus. J Invest Dermatol 119:433–439

Barland CO, Elias PM, Ghadially R (2005) The aged epidermal barrier: basis for functional abnormalities. In: Elias PM, Feingold KR (eds) Skin barrier. Marcel Dekker, New York, pp 535–552

Behne MJ, Meyer JW, Hanson KM, Barry NP, Murata S, Crumrine D, Clegg RW, Gratton E, Holleran WM, Elias PM, Mauro TM (2002) NHE1 regulates the stratum corneum permeability barrier homeostasis. Microenvironment acidification assessed with fluorescence lifetime imaging. J Biol Chem 277:47399–47406

Behne MJ, Barry NP, Hanson KM, Aronchik I, Clegg RW, Gratton E, Feingold K, Holleran WM, Elias PM, Mauro TM (2003) Neonatal development of the stratum corneum pH gradient: localization and mechanisms leading to emergence of optimal barrier function. J Invest Dermatol 120:998–1006

Bibel DJ, Miller SJ, Brown BE, Pandey BB, Elias PM, Shinefield HR, Aly R (1989) Antimicrobial activity of stratum corneum lipids from normal and essential fatty acid-deficient mice. J Invest Dermatol 92:632–638

Bibel DJ, Aly R, Shinefield HR (1992) Antimicrobial activity of sphingosines. J Invest Dermatol 98:269–273

Braff MH, Di Nardo A, Gallo RL (2005) Keratinocytes store the antimicrobial peptide cathelicidin in lamellar bodies. J Invest Dermatol 124:394–400

Braff MH, Gallo RL (2006) Antimicrobial peptides: an essential component of the skin defensive barrier. Curr Top Microbiol Immunol 306:91–110

Brattsand M, Stefansson K, Lundh C, Haasum Y, Egelrud T (2005) A proteolytic cascade of kallikreins in the stratum corneum. J Invest Dermatol 124:198–203

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 47:198–208

Choi EH, Brown BE, Crumrine D, Chang S, Man MQ, Elias PM, Feingold KR (2005) Mechanisms by which psychologic stress alters cutaneous permeability barrier homeostasis and stratum corneum integrity. J Invest Dermatol 124:587–595

Choi EH, Man MQ, Wang F, Zhang X, Brown BE, Feingold KR, Elias PM (2005) Is endogenous glycerol a determinant of stratum corneum hydration in humans? J Invest Dermatol 125:288–293

Choi EH, Demerjian M, Crumrine D, Brown BE, Mauro T, Elias PM, Feingold KR (2006) Glucocorticoid blockade reverses psychological stress-induced abnormalities in epidermal structure and function. Am J Physiol Regul Integr Comp Physiol 291:R1657–R1662

Choi EH, Crumrine D, Xu P, Man MQ, Elias PM, Mauro TM (2007) Stratum corneum acidification is impaired in moderately aged human and murine skin, leading to impaired barrier function. J Invest Dermatol (in press)

Christophers E, Kligman AM (1964) Visualization of the cell layers of the stratum corneum. J Invest Dermatol 42:407–409

de Jongh GJ, Zeeuwen PL, Kucharekova M, Pfundt R, van der Valk PG, Blokx W, Dogan A, Hiemstra PS, van de Kerkhof PC, Schalkwijk J (2005) High expression levels of keratinocyte antimicrobial proteins in psoriasis compared with atopic dermatitis. J Invest Dermatol 125:1163–1173

Denda M, Tsuchiya T, Elias PM, Feingold KR (2000) Stress alters cutaneous permeability barrier homeostasis. Am J Physiol Regul Integr Comp Physiol 278:R367–R372

Eckert RL, Lee KC (2006) S100A7 (psoriasin): a story of mice and men. J Invest Dermatol 126:1442–1444

Elias PM, Friend DS (1975) The permeability barrier in mammalian epidermis. J Cell Biol 65:180–191

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

Elias PM, Menon GK (1991) Structural and lipid biochemical correlates of the epidermal permeability barrier. Adv Lipid Res 24:1–26

Elias PM (1996) Stratum corneum architecture, metabolic activity and interactivity with subjacent cell layers. Exp Dermatol 5:191–201

Elias PM, Cullander C, Mauro T, Rassner U, Komuves L, Brown BE, Menon GK (1998) The secretory granular cell: the outermost granular cell as a specialized secretory cell. J Investig Dermatol Symp Proc 3:87–100

Elias PM, Feingold KR (2001) Coordinate regulation of epidermal differentiation and barrier homeostasis. Skin Pharmacol Appl Skin Physiol 14 (Suppl 1):28–34

Elias PM (2005) Stratum corneum defensive functions: an integrated view. J Invest Dermatol 125:183–200

Elias PM, Choi EH (2005) Interactions among stratum corneum defensive functions. Exp Dermatol 14:719–726

Elias PM, Crumrine D, Rassner U, Menon GK, Feingold KR, William ML (2006) Pathogenesis of desquamation and permeability barrier abnormalities in RXLI. Skin Barrier 511–518

Fartasch M, Diepgen TL (1992) The barrier function in atopic dry skin. Disturbance of membrane-coating granule exocytosis and formation of epidermal lipids? Acta Derm Venereol (Stockh) Suppl 176:26–31

Feingold KR (1991) The regulation and role of epidermal lipid synthesis. Adv Lipid Res 24:57–82

Fluhr JW, Kao J, Jain M, Ahn SK, Feingold KR, Elias PM (2001) Generation of free fatty acids from phospholipids regulates stratum corneum acidification and integrity. J Invest Dermatol 117:44–51

Fluhr JW, Elias PM (2002) Stratum corneum pH: Formation and function of the ‘acid mantle.’ Exog Dermatol 1:163–175

Fluhr JW, Mao-Qiang M, Brown BE, Wertz PW, Crumrine D, Sundberg JP, Feingold KR, Elias PM (2003) Glycerol regulates stratum corneum hydration in sebaceous gland deficient (asebia) mice. J Invest Dermatol 120:728–737

Fluhr JW, Behne MJ, Brown BE, Moskowitz DG, Selden C, Mao-Qiang M, Mauro TM, Elias PM, Feingold KR (2004) Stratum corneum acidification in neonatal skin: secretory phospholipase A2 and the sodium/hydrogen antiporter-1 acidify neonatal rat stratum corneum. J Invest Dermatol 122:320–329

Ganz T (2003) Defensins: antimicrobial peptides of innate immunity. Nat Rev Immunol 3:710–720

Glaser R, Harder J, Lange H, Bartels J, Christophers E, Schroder JM (2005) Antimicrobial psoriasin (S100A7) protects human skin from Escherichia coli infection. Nat Immunol 6:57–64

Hachem JP, Crumrine D, Fluhr J, Brown BE, Feingold KR, Elias PM (2003) pH directly regulates epidermal permeability barrier homeostasis, and stratum corneum integrity/cohesion. J Invest Dermatol 121:345–353

Hachem JP, Man MQ, Crumrine D, Uchida Y, Brown BE, Rogiers V, Roseeuw D, Feingold KR, Elias PM (2005) Sustained serine proteases activity by prolonged increase in pH leads to degradation of lipid processing enzymes and profound alterations of barrier function and stratum corneum integrity. J Invest Dermatol 125:510–520

Hachem JP, Schurer N, Roelandt T, Pu X, Guiddelo C, Man M-Q, Crumrine D, Feingold KR, Mauro T, Elias PM (2007) Hyperacidification of stratum corneum produces a ‘super-barrier’ in normal human and rodent skin. J Invest Dermatol (in press)

Haftek M, Simon M, Kanitakis J, Marechal S, Claudy A, Serre G, Schmitt D (1997) Expression of corneodesmosin in the granular layer and stratum corneum of normal and diseased epidermis. Br J Dermatol 137:864–873

Hara-Chikuma M, Verkman AS (2006) Physiological roles of glycerol-transporting aquaporins: the aquaglyceroporins. Cell Mol Life Sci 63:1386–1392

Harder J, Schroder JM (2002) RNase 7, a novel innate immune defense antimicrobial protein of healthy human skin. J Biol Chem 277:46779–46784

Harder J, Meyer-Hoffert U, Wehkamp K, Schwichtenberg L, Schroder JM (2004) Differential gene induction of human beta-defensins (hBD-1, -2, -3, and -4) in keratinocytes is inhibited by retinoic acid. J Invest Dermatol 123:522–529

Hou SY, Mitra AK, White SH, Menon GK, Ghadially R, Elias PM (1991) Membrane structures in normal and essential fatty acid-deficient stratum corneum: characterization by ruthenium tetroxide staining and X-ray diffraction. J Invest Dermatol 96:215–223

Houben E, Holleran WM, Yaginuma T, Mao C, Obeid LM, Rogiers V, Takagi Y, Elias PM, Uchida Y (2006) Differentiation-associated expression of ceramidase isoforms in cultured keratinocytes and epidermis. J Lipid Res 47:1063–1070

Izadpanah A, Gallo RL (2005) Antimicrobial peptides. J Am Acad Dermatol 52:381–390

Jensen JM, Schutze S, Forl M, Kronke M, Proksch E (1999) Roles for tumor necrosis factor receptor p55 and sphingomyelinase in repairing the cutaneous permeability barrier. J Clin Invest 104:1761–1770

Kao JS, Fluhr JW, Man MQ, Fowler AJ, Hachem JP, Crumrine D, Ahn SK, Brown BE, Elias PM, Feingold KR (2003) Short-term glucocorticoid treatment compromises both permeability barrier homeostasis and stratum corneum integrity: inhibition of epidermal lipid synthesis accounts for functional abnormalities. J Invest Dermatol 120:456–464

Korting HC, Kober M, Mueller M, Braun-Falco O (1987) Influence of repeated washings with soap and synthetic detergents on pH and resident flora of the skin of forehead and forearm. Results of a cross-over trial in health probationers. Acta Derm Venereol 67:41–47

Korting HC, Hubner K, Greiner K, Hamm G, Braun-Falco O (1990) Differences in the skin surface pH and bacterial microflora due to the long-term application of synthetic detergent preparations of pH 5.5 and pH 7.0. Results of a crossover trial in healthy volunteers. Acta Derm Venereol 70:429–431

Krien P, Kermici M (2000) Evidence for the existence of a self-regulated enzymatic process within human stratum corneum—an unexpected role for urocanic acid. J Invest Dermatol 115:414–420

Lehrer RI (2004) Primate defensins. Nat Rev Microbiol 2:727–738

Mackenzie IC (1975) Ordered structure of the epidermis. J Invest Dermatol 65:45–51

Mao-Qiang M, Elias PM, Feingold KR (1993) Fatty acids are required for epidermal permeability barrier function. J Clin Invest 92:791–798

Mao-Qiang M, Feingold KR, Jain M, Elias PM (1995) Extracellular processing of phospholipids is required for permeability barrier homeostasis. J Lipid Res 36:1925–1935

Mao-Qiang M, Jain M, Feingold KR, Elias PM (1996) Secretory phospholipase A2 activity is required for permeability barrier homeostasis. J Invest Dermatol 106:57–63

Marchionini A, Hausknecht W (1938) Sauremantel der haut and bakterienabwehr. Klin Wochenschr 17:663–666

Martinsson H, Yhr M, Enerback C (2005) Expression patterns of S100A7 (psoriasin) and S100A9 (calgranulin-B) in keratinocyte differentiation. Exp Dermatol 14:161–168

Menon GK, Feingold KR, Elias PM (1992) Lamellar body secretory response to barrier disruption. J Invest Dermatol 98:279–289

Menon GK, Elias PM (1997) Morphologic basis for a pore-pathway in mammalian stratum corneum. Skin Pharmacol 10:235–246

Menton DN, Eisen AZ (1971) Structure and organization of mammalian stratum corneum. J Ultrastruct Res 35:247–264

Miller SJ, Aly R, Shinefeld HR, Elias PM (1988) In vitro and in vivo antistaphylococcal activity of human stratum corneum lipids. Arch Dermatol 124:209–215

Monod M, Capoccia S, Lechenne B, Zaugg C, Holdom M, Jousson O (2002) Secreted proteases from pathogenic fungi. Int J Med Microbiol 292:405–419

Nizet V, Ohtake T, Lauth X, Trowbridge J, Rudisill J, Dorschner RA, Pestonjamasp V, Piraino J, Huttner K, Gallo RL (2001) Innate antimicrobial peptide protects the skin from invasive bacterial infection. Nature 414:454–457

Nylander-Lundqvist E, Egelrud T (1997) Formation of active IL-1 beta from pro-IL-1 beta catalyzed by stratum corneum chymotryptic enzyme in vitro. Acta Derm Venereol 77:203–206

Oren A, Ganz T, Liu L, Meerloo T (2003) In human epidermis, beta-defensin 2 is packaged in lamellar bodies. Exp Mol Pathol 74:180–182

Oren Z, Lerman JC, Gudmundsson GH, Agerberth B, Shai Y (1999) Structure and organization of the human antimicrobial peptide LL-37 in phospholipid membranes: relevance to the molecular basis for its non-cell-selective activity. Biochem J 341(Pt 3):501–513

Radin NS (2006) Preventing the binding of pathogens to the host by controlling sphingolipid metabolism. Microbes Infect 8:938–945

Rassner U, Feingold KR, Crumrine DA, Elias PM (1999) Coordinate assembly of lipids and enzyme proteins into epidermal lamellar bodies. Tissue Cell 31:489–498

Schaller M, Schackert C, Korting HC, Januschke E, Hube B (2000) Invasion of Candida albicans correlates with expression of secreted aspartic proteinases during experimental infection of human epidermis. J Invest Dermatol 114:712–717

Schmidtchen A, Frick IM, Andersson E, Tapper H, Bjorck L (2002) Proteinases of common pathogenic bacteria degrade and inactivate the antibacterial peptide LL-37. Mol Microbiol 46:157–168

Schmuth M, Fluhr JW, Crumrine DC, Uchida Y, Hachem JP, Behne M, Moskowitz DG, Christiano AM, Feingold KR, Elias PM (2004) Structural and functional consequences of loricrin mutations in human loricrin keratoderma (Vohwinkel syndrome with ichthyosis). J Invest Dermatol 122:909–922

Schroder JM, Harder J (2006) Antimicrobial skin peptides and proteins. Cell Mol Life Sci 63:469–486

Scott IR, Harding CR (1986) Filaggrin breakdown to water binding compounds during development of the rat stratum corneum is controlled by the water activity of the environment. Dev Biol 115:84–92

Serre G, Mils V, Haftek M, Vincent C, Croute F, Reano A, Ouhayoun JP, Bettinger S, Soleilhavoup JP (1991) Identification of late differentiation antigens of human cornified epithelia, expressed in re-organized desmosomes and bound to cross-linked envelope. J Invest Dermatol 97:1061–1072

Strober W (2006) Immunology. Unraveling gut inflammation. Science 313:1052–1054

Thormar H, Isaacs CE, Brown HR, Barshatzky MR, Pessolano T (1987) Inactivation of enveloped viruses and killing of cells by fatty acids and monoglycerides. Antimicrob Agents Chemother 31:27–31

Tsai JC, Guy RH, Thornfeldt CR, Gao WN, Feingold KR, Elias PM (1996) Metabolic approaches to enhance transdermal drug delivery, 1. Effect of lipid synthesis inhibitors. J Pharm Sci 85:643–648

Uchida Y, Hara M, Nishio H, Sidransky E, Inoue S, Otsuka F, Suzuki A, Elias PM, Holleran WM, Hamanaka S (2000) Epidermal sphingomyelins are precursors for selected stratum corneum ceramides. J Lipid Res 41:2071–2082

Viani FC, Dos Santos JI, Paula CR, Larson CE, Gambale W (2001) Production of extracellular enzymes by Microsporum canis and their role in its virulence. Med Mycol 39:463–468

Warner RR, Myers MC, Taylor DA (1988) Electron probe analysis of human skin: determination of the water concentration profile. J Invest Dermatol 90:218–224

Weber G, Heilborn JD, Chamorro Jimenez CI, Hammarsjo A, Torma H, Stahle M (2005) Vitamin D induces the antimicrobial protein hCAP18 in human skin. J Invest Dermatol 124:1080–1082

Wille JJ, Kydonieus A (2003) Palmitoleic acid isomer (C16:1delta6) in human skin sebum is effective against gram-positive bacteria. Skin Pharmacol Appl Skin Physiol 16:176–187

Ye J, Garg A, Calhoun C, Feingold KR, Elias PM, Ghadially R (2002) Alterations in cytokine regulation in aged epidermis: implications for permeability barrier homeostasis and inflammation, I. IL-1 gene family. Exp Dermatol 11:209–216