Abstract
The epidermis, primarily made of keratinocytes, is continuously renewed by the proliferation of stem cells and the differentiation of their progeny, which undergo terminal differentiation as they leave the basal layer and move upward toward the surface, where they die and slough off. These cells are responsible for tissue homeostasis and regeneration of epidermis following injury. Basal keratinocytes append the dermal epidermal junction, a cell surface-associated extracellular matrix that provides structural support to keratinocytes and influences their behaviour. Similar to all basement membranes, the dermal epidermal junction primarily consists of laminins, type IV collagens, nidogens, and the heparan sulfate proteoglycan perlecan, all of which are necessary for tissue organization and structural integrity. Keratinocytes committed to the differentiation program downregulate integrins to become less adhesive, move to the suprabasal compartment and continue their upward movement until they are terminally differentiated and shed off. This produces several layers of keratinocytes, at different stages of differentiation that can be identified by the expression of keratins. Beside a function of protective barrier, epidermis has also an important secretory activity. The numerous and diverse factors produced by keratinocytes, that may act in an autocrine, paracrine or endocrine manner, are described in this chapter.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Similar content being viewed by others
References
Aubin F. Skin immune system. In: Handbook of Measuring the skin. 1st edn. Berlin: Springer; 2004.
Bae S, Matsunaga Y, Tanaka Y, Katayama I. Autocrine induction of substance P mRNA and peptide in cultured normal human keratinocytes. Biochem Biophys Res Commun. 1999;263:327–33.
Barrandon Y, Green H. Cell size as a determinant of the clone-forming ability of human keratinocytes. Proc Natl Acad Sci U S A. 1985;82:5390–4.
Barrandon Y, Green H. Three clonal types of keratinocyte with different capacities for multiplication. Proc Natl Acad Sci U S A. 1987;84:2302–6.
Bos JD, Kapsenberg ML. The skin immune system: progress in cutaneous biology. Immun Today. 1993;14:75–8.
Boxman IL, Ruwhof C, Boerman OC, Lowik CW, Ponec M. Role of fibroblasts in the regulation of proinflammatory interleukin IL-1, IL-6 and IL-8 levels induced by keratinocyte derived IL-1. Arch Dermatol Res. 1996;288:391–8.
Boyce ST. Epidermis as a secretory tissue. J Invest Dermatol. 1994;102:8–10.
Brouard M, Casado M, Djelidi S, Barrandon Y, Farman N. Epithelial sodium channel in human epidermal keratinocytes: expression of its subunits and relation to sodium transport and differentiation. J Cell Sci. 1999;112:3343–52.
Deliconstantinos G, Villiotou V, Stravrides JC. Release by ultraviolet B (u.v.B) radiation of nitric oxide (NO) from human keratinocytes: a potential role for nitric oxide in erythema production. Br J Pharmacol. 1995;114:1257–65.
Dorschner RA, Pestonjamasp VK, Tamakuwala S, Ohtake T, Rudisill J, Nizet V, Agerberth B, Gudmundsson GH, Gallo RL. Cutaneous injury induces the release of cathelicidin anti-microbial peptides active against group A Streptococcus. J Invest Dermatol. 2001;117:91–7.
Eming SA, Medalie DA, Tompkins RG, Yarmush ML, Morgan JR. Genetically modified human keratinocytes overexpressing PDGF-A enhance the performance of a composite skin graft. Hum Gene Ther. 1998;9:529–39.
Fenjves ES, Gordon DA, Pershing LK, Williams DL, Taichman LB. Systemic distribution of apolipoprotein E secreted by grafts of epidermal keratinocytes: implications for epidermal function and gene therapy. Proc Natl Acad Sci U S A. 1989;86:8803–7.
Harder J, Bartels J, Christophers E, Schroder J-M. A peptide antibiotic from human skin. Nature. 1997;6636:387–861.
Heenen M, Galand P. The growth fraction of normal human epidermis. Dermatology. 1997;194:313–7.
Holick MF. Skin: site of the synthesis of vitamin D and a target tissue for the active form, 1,25-Dihydroxyvitamin D3. In: Milestone LM, Edelson RL, editors. Endocrine, metabolic and immunologic functions of keratinocytes, vol. 548. New York: Annals of the New York Academy of Sciences; 1988. p. 14–26.
Holtz J. Hemodynamics in regional circulatory beds and local vascular reactivity. In: Greger R, Windhorst U, editors. Comprehensive human physiology. From cellular mechanisms to integration, vol. 2. Berlin: Springer; 1996. p. 1917–40.
Insogna KL, Stewart AF, Ikeda K, Centrella M, Milestone LM. Characterization of a parathyroid hormone-like peptide secreted by human keratinocytes. In: Milestone LM, Edelson RL, editors. Endocrine, metabolic and immunologic functions of keratinocytes, vol. 548. Ney York: Annals of the New York Academy of Sciences; 1988. p. 146–59.
Jensen UB, Lowel S, Watt FM. The spatial relationship between stem cells and their progeny in the basal layer of human epidermis: a new view based on whole-mount labelling and lineage analysis. Development. 1999;126:2409–18.
Kaplan MM, Gordon PR, Pan C, Lee JK, Gilchrest BA. Keratinocytes convert thyroxine to triiodothyronine. In: Milestone LM, Edelson RL, editors. Endocrine, metabolic and immunologic functions of keratinocytes, vol. 548. New York: Annals of the New York Academy of Sciences; 1988. p. 56–65.
Katz AB, Taichman LB. Epidermis as a secretory tissue: an in vitro model to study keratinocyte secretion. J Invest Dermatol. 1994;102:55–60.
Katz AB, Taichman LB. A partial catalog of proteins secreted by epidermal keratinocytes in culture. J Invest Dermatol. 1999;112:818–21.
Kaur P, Li A. Adhesive properties of human basal epidermal cells: an analysis of keratinocyte stem cells, transit amplifying cells and postmitotic differentiating cells. J Invest Dermatol. 2000;114:413–20.
Krueger GG, Morgan JR, Jorgensen CM, Schmidt L, Li HL, Kwan MK, Boyce ST, Wiley HS, Kaplan J, Petersen MJ. Genetically modified skin to treat disease: potential and limitations. J Invest Dermatol. 1994;103:76S–84.
Kupper TS. The activated keratinocyte: a model for inducible cytokine production by none-bone marrow-derived cells in cutaneous inflammatory and immune responses. J Invest Dermatol. 1990;94:146S–50.
Levy L, Broad S, Diekmann D, Evans RD, Watt FM. Beta 1 integrins regulate keratinocyte adhesion and differentiation. Mol Biol Cell. 2000;11:453–66.
Malaviya R, Morrisson AR, Pentland AP. Histamine in human epidermal cells is induced by ultraviolet light injury. J Invest Dermatol. 1996;106:785–9.
Martinez A, Elsasser TH, Muro-Cacho C, Moody TW, Miller MJ, Macri CJ, Cuttitta F. Expression of adrenomedullin and its receptor in normal and malignant human skin: a potential pluripotent role in the integument. Endocrinology. 1997;138:5597–604.
Maruyama K, Zhang JZ, Nihei Y, Ono I, Kaneko F. Regulatory effects of gamma interferon on IL-6 and IL-8 secretion by cultured human keratinocytes and dermal fibroblasts. J Dermatol. 1995;22:901–6.
Mazereeuw Hautier J, Redoules D, Tarroux R, Charveron M, Salles JP, Simon MF, Cerutti I, Assalit MF, Gall Y, Bonafe JL, Chap H. Identification of pancreatic type I secreted phospholipase A2 in human epidermis and its determination by tape striping. Br J Dermatol. 2000;142:424–31.
Michel M, Torok N, Godbout MJ, Luissier M, Gaudreau P, Royal A, Germain L. Keratin 19 as a biochemical marker of skin stem cells in vivo and in vitro: keratin 19 expressing cells are differentially localized in function of anatomic sites, and their number varies with donor age and culture stage. J Cell Sci. 1996;109:1017–28.
Nathan C, Sporn M. Cytokines in context. J Cell Biol. 1991;113:981–6.
Nizet V, Ohtake T, Lauth X, Trowbridge J, Rudisill J, Dorschner RA, Pestonjamasp V, Piraino J, Huttner K, Gallo RL. Innate antimicrobial peptide protects the skin from invasive bacterial infection. Nature. 2001;414:454–7.
Oda Y, Imanzahrai A, Kwong A, Komuves L, Elias PM, Largman C, Mauro T. Epithelial sodium channels are upregulated during epidermal differentiation. J Invest Dermatol. 1999;113:796–801.
Ong PY, Ohtake T, Brandt C, Strickland I, Boguniewicz M, Ganz T, Gallo RL, Leung DYM. Endogenous antimicrobial peptides and skin infections in atopic dermatitis. N Engl J Med. 2002;347:1151–60.
Reinartz J, Bechtel MJ, Kramer MD. Tumor necrosis factor alpha induced apoptosis in a human keratinocyte cell line (HaCat) is counteracted by transforming growth factor alpha. Exp Cell Res. 1996;228:334–40.
Rys-Sikora KE, Konger RL, Schoggins JW, Malaviya R, Pentland AP. Coordinate expression of secretory phospholipase A(2) and cyclooxygenase-2 in activated human keratinocytes. Am J Physiol Cell Physiol. 2000;278:C822–33.
Schauer E, Trautinger F, Köck A, Schwarz A, Bhardwaj R, Simon M, Ansel JC, Schwarz T, Luger TA. Proopiomelanocortin derived peptides are synthesized and released by human keratinocytes. J Clin Invest. 1994;93:2258–62.
Schröder JM. Cytokine networks in the skin. J Invest Dermatol. 1995;105:20S–4.
Shimizu Y, Sakai M, Umemura Y, Ueda H. Immunohistochemical localization of nitric oxide synthase in normal human skin: expression of endothelial-type and inducible-type nitric oxide synthase in keratinocytes. J Dermatol. 1997;24:80–7.
Stoof TJ, Boorsma DM, Nickoloff BJ. Keratinocyte and immunological cytokines. In: Leigh IM, Lane EB, Watt FM, editors. The keratinocyte handbook. Cambridge: Cambridge University Press; 1994. p. 235–42.
Watt FM, Hogan BLM. Out of Eden: stem cells and their niches. Science. 2000;287:1427–30.
Wiedow O, Harder J, Bartels J, Streit V, Christopher E. Antileukoprotease in human skin: an antibiotic peptide constitutively produced by keratinocytes. Biochem Biophys Res Commun. 1998;248:904–9.
Wysolmerski JJ, Stewart AF. The physiology of parathyroid hormone-related protein: an emerging role as a developmental factor. Annu Rev Physiol. 1998;60:431–60.
Zhu AJ, Watt FM. Beta-catenin signalling modulates proliferative potential of human epidermal keratinocytes independently of intercellular adhesion. Development. 1999;126:2285–98.
Zhu AJ, Haase I, Watt FM. Signaling via beta1 integrins and mitogen-activated protein kinase determines human epidermal stem cell fate in vitro. Proc Natl Acad Sci U S A. 1999;96:6728–33.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Glossary
- ACTH
-
Adrenocorticotrophic hormone
- Autocrine
-
Peptides (cytokine, extracellular matrix components, epidermal proteins etc.) are released but bind immediately to receptors and act on the cell that produced them.
- Contra IL-1
-
Contra interleukin 1
- Endocrine
-
Peptides, synthesized by the keratinocytes, enter the circulation and induce specific biologic responses in distant target tissues.
- Exocrine
-
Release of secretion toward the external part of the body. Glandular epithelia (sebaceous and sweat) of the skin are specialized for this function.
- FGF
-
Fibroblast growth factor. Either acid FGF or basic FGF
- GCSF
-
Granulocyte colony-stimulating factor
- GMCSF
-
Granulocyte-/macrophage-stimulating factor
- Homeostasis
-
Maintenance of the organism’s physiological parameters at their normal value
- huGRO
-
Human growth factor
- IL
-
Interleukin: IL-1α, interleukin 1α; IL-1β, interleukin 1 β; IL-1ra, interleukin 1 receptor antagonist; IL-6, interleukin 6
- IFNγ-IP10
-
Interferon gamma-induced protein
- Juxtacrine
-
Peptides are released and will act on cells in contact with the producing cell.
- KGF
-
Keratinocyte growth factor
- K LIF
-
Keratinocyte-derived lymphocyte inhibitory factor
- MCAF
-
Monocyte chemotactic and activating factor
- MCSF
-
Macrophage colony-stimulating factor
- MSH
-
Melanocyte-stimulating hormone
- NGF
-
Nerve growth factor
- Paracrine
-
Peptides are released by a cell and will act on cells immediately surrounding the producing cell.
- PDGF
-
Platelet-derived growth factor
- TGFα
-
Transforming growth factor alpha
- TGFβ1
-
Transforming growth factor beta1
- TNFα
-
Tumor necrosis factor alpha
Rights and permissions
Copyright information
© 2017 Springer International Publishing Switzerland
About this entry
Cite this entry
Rousselle, P., Gentilhomme, E., Neveux, Y. (2017). Epidermal Physiology. In: Humbert, P., Fanian, F., Maibach, H., Agache, P. (eds) Agache's Measuring the Skin. Springer, Cham. https://doi.org/10.1007/978-3-319-32383-1_36
Download citation
DOI: https://doi.org/10.1007/978-3-319-32383-1_36
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-319-32381-7
Online ISBN: 978-3-319-32383-1
eBook Packages: MedicineReference Module Medicine