Clinical and Laboratory Investigations
Changes in Keratin 6 and Keratin 10 (Co-)Expression in Lesional and Symptomless Skin of Spreading PsoriasisMommers J.M. · van Rossum M.M. · van Erp P.E.J. · van de Kerkhof P.C.M.
Department of Dermatology, University Medical Centre Nijmegen, The Netherlands
Do you have an account?
- Rent for 48h to view
- Buy Cloud Access for unlimited viewing via different devices
- Synchronizing in the ReadCube Cloud
- Printing and saving restrictions apply
Rental: USD 8.50
Cloud: USD 20.00
Background: Keratin 6 (K6) and keratin 10 (K10) are markers for epidermal hyperproliferation and differentiation, respectively, and are both expressed in the suprabasal layers of the epidermis. They may be co-expressed in different stages of the spreading psoriatic lesion, but single expression can also occur. Objective: To investigate to what extent keratinocytes express K6 and K10, and to what extent they co-express K6 and K10 in different stages of the psoriatic lesion. We studied this in spreading psoriatic plaques. Methods: Three 3-mm punch biopsies were obtained from the inner involved margin of a spreading lesion, from the uninvolved skin immediately adjacent to the spreading plaque, and from the distant uninvolved skin of 8 patients with incipient psoriasis. From 9 healthy volunteers, 3-mm punch biopsies were obtained as controls. After preparation of single cell suspensions of these biopsies, a triple staining protocol was performed with markers for K6 (monoclonal antibody LHK6B), K10 (monoclonal antibody RKSE60) and DNA content (TO-PRO-3 iodide). Subsequently, cells were measured with a flow cytometer and the proportion of the markers was calculated using specific software. Results: We observed a population of K6/K10-co-expressing cells, but also populations expressing only K6. These subpopulations varied with the involvement of the lesion. There was a statistically significant difference between the inner margin and the outer margin with respect to the proportion of K6- and K10-expressing cells, whereas more K6-positive and K10-negative cells were detected in the inner margin of the lesions. The proportion of K6/K10-co-expressing cells in the inner margin was significantly different from the distant uninvolved skin. Conclusion: We confirmed that individual keratinocytes in psoriasis can express K6 or K10 depending on their localization in involved or uninvolved skin. There is a unique subpopulation of cells in the psoriatic plaques which co-express K6 and K10. More studies are required to fully understand the pathogenic relevance of co-expression and single expression of K6 and K10.
© 2000 S. Karger AG, Basel
- Leigh IM, Purkis PE, Whitehead P, Lane EB: Monospecific monoclonal antibodies to keratin 1 carboxy terminal (synthetic peptide) and to keratin 10 as markers of epidermal differentiation. Br J Dermatol 1993;129:110–119.
- van Erp PEJ, Rijzewijk JJ, Boezeman JBM, Leenders J, de Mare S, Schalkwijk J, van de Kerkhof PCM, Ramaekers FC, Bauer FW: Flow cytometric analysis of epidermal subpopulations from normal and psoriatic skin using monoclonal antibodies against intermediate filaments. Am J Pathol 1989;135:865–870.
- Kim KH, Marchuk D, Fuchs E: Expression of unusually large keratins during terminal differentiation: Balance of type I and type II keratins is not disrupted. J Cell Biol 1984;99:1872–1977.
- Weiss RA, Eichner R, Sun TT: Monoclonal antibody analysis of keratin expression in epidermal disease: A 48- and 56-kilodalton keratin as molecular markers for hyperproliferative keratinocytes. J Cell Biol 1984;98:1397–1406.
- McKay IA, Leigh IM: Altered keratinocyte growth and differentiation in psoriasis. Clin Dermatol 1995;13:105–114.
- de Mare S, de Jong EMGJ, van Erp PEJ, van de Kerkhof PCM: Markers for proliferation and keratinization in the margin of the active psoriatic lesion. Br J Dermatol 1990;122:469–475.
- Hsuzar M, Gig-Leitner O, Moll R, Franke WW, Geiger B: Monoclonal antibodies to various acidic (type I) cytokeratins of stratified eptihelia: Selective markers for stratification and squamous cell carcinomas. Differentiation 1986;31:141–153.
- De Mare S, van Erp PEJ, Ramaekers FC, van de Kerkhof PCM: Flow cytometric quantification of human epidermal cells expressing keratin 16 in vivo after standardized trauma. Arch Dermatol Res 1990;282:126–130.
Mommers JM, Goossen JW, van Erp PEJ, van de Kerkhof PCM: A novel functional multiparameter flow cytometric assay to characterize proliferation in skin. Commun Clin Cytometry 2000;42:43–49.
- Galvin S, Loomis C, Manabe M, Dhouailly D, Sun TT: The major pathways of keratinocyte differentiation as defined by keratin expression: An overview. Adv Dermatol 1989;4:277–299.
- van de Kerkhof PCM, Gerritsen MJP, de Jong EMGJ: Transition from symptomless to lesional psoriatic skin. Clin Exp Dermatol 1996;21:325–329.
- Glade CP, Seegers BAMPA, Meulen EF, van Hoojdonk CAEM, van Erp PEJ, van de Kerkhof PCM: Multiparameter flow cytometric charcterization of epidermal cell suspensions prepared from normal and hyperproliferative human skin using an optimized thermolysin-trypsin protocol. Arch Dermatol Res 1996;288:203–210.
- Leigh IM, Pulford KA, Ramaekers FC, Lane EB: Psoriasis: Maintenance of an intact monolayer basal cell differentiation compartment in spite of hyperproliferation. Br J Dermatol 1985;113:53–64.
- Jiang CK, Magnaldo T, Othsuki M, Freedberg IM, Bernerd F, Blumenberg M: Epidermal growth factor and transforming growth factor alpha specifically induce the acitvation- and hyperproliferation-associated keratins 6 and 16. Proc Natl Acad Sci USA 1993;90:6786–6790.
- Navarro JM, Casatorres J, Jorcano JL: Elements controlling the expression and induction of the skin hyperproliferation-associated keratin K6. J Biol Chem 1995;270:21362–21367.
- Yoshikawa K, Katagata Y, Kondo S: Relative amounts of keratin 17 are higher than those of keratin 16 in hair-follicle-derived tumors in comparison with nonfollicular epithelial skin tumors. J Invest Dermatol 1995;104:396–400.
- Swensson O, Langbein L, McMillan JR, Stevens HP, Leigh IM, McLean WH, Lane EB, Eady RA: Specialized keratin expression pattern in human ridged skin as an adaptation to high physical stress. Br J Dermatol 1998;139:767–775.
- van Hooijdonk CAEM, Clade CP, van Erp PEJ: TO-PRO-3 iodide: A novel HeNe laser-excitable DNA stain as an alternative for propidium iodide in multiparameter flow cytometry. Cytometry 1994;17:185–189.
- Rulo HF, van Vijmen-Willems IMJJ, Schalkwijk J, Verstraeten AA, van de Kerkhof PCM: Normal human skin demonstrates marked site-variation of tenascin expression, not correlated to epidermal proliferation (Ki-67 binding). J Dermatol Sci 1993;5:54–57.
- Swensson O, Eady RA: Morphology of the keratin filament network in palm and sole skin: Evidence for site-dependent features based on stereological analysis. Arch Dermatol Res 1996;288:55–62.
- Glade CP, Botermans RJ, van Erp PEJ, van de Kerkhof PCM: The dynamics of the response of normal skin to single and multiple epicutaneous leukotriene B4 appliactions analysed by three-colour flow cytometry. Acta Derm Venereol 1995;75:437–441.
- van Rossum MM, Mommers JM, van Hooijdonk CAEM, van Erp PEJ, van de Kerkhof PCM: The response of distant uninvolved psoriatic skin to standardised injury is not different from that in normal skin. Skin Pharmacol Appl Skin Physiol 1999;12:271–275.
Article / Publication Details
Copyright / Drug Dosage / DisclaimerCopyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.