Abstract
Netherton syndrome (NS) is an orphan genetic skin disease with a profound skin barrier defect and severe allergic manifestations. NS is caused by loss of function mutations in SPINK5 encoding lympho-epithelial Kazal-type inhibitor (LEKTI), a secreted multi-domain serine protease inhibitor expressed in stratified epithelia. Studies in mouse models and in NS patients have established that unopposed kallikrein 5 activity triggers stratum corneum detachment and activates PAR-2 signaling, leading to the autonomous production of pro-allergic and pro-inflammatory mediators. This emerging knowledge on NS pathogenesis has highlighted a central role for protease regulation in skin homeostasis but also in the complexity of the disease, and holds the promise of new specific treatments.
About the authors
Laetitia Furio is a post-doctoral fellow at University Paris Descartes-Paris Sorbonne Cité at Imagine Institute in Paris, France. She completed her PhD on cutaneous immunology in 2008. In 2010, she joined Alain Hovnanian’s group to work on a severe genetic skin disease called Netherton syndrome (NS). To better understand NS pathophysiology, she has been developing and characterizing several new murine models for NS and has performed detailed clinical and biological investigations of a large cohort of NS patients.
Alain Hovnanian is full professor of Dermatology and Genetics at the new ‘Institut Hospitalo-Universitaire’ (IHU) at Necker hospital in Paris. He runs a translational clinic on genetic skin diseases of children and adults at Necker hospital for Sick Children. He is the director of a diagnostic and research laboratory at INSERM UMR 1163 on genetic skin diseases at the Imagine Institute for genetic diseases.The central theme of his research. is the development of translational research to improve the understanding and treatment of severe genetic skin diseases. Following the identification of the SPINK5 gene encoding the LEKTI protease inhibitor as the defective gene in Netherton syndrome (NS), his group has developed several murine models for NS in order to dissect the roles of proteases and their inhibitors in the biological cascades involved in the disease. This work has placed epidermal kallikreins at the center of skin inflammation and allergy in NS and has led to the identification of new therapeutic targets. Currently, his research aims at improving our understanding on NS and other inflammatory skin diseases in order to design innovative and efficient therapies. He has published over 200 research articles, review articles and book chapters. Photograph: Copyright © Laurent Attias/Fondation Imagine.
References
Alef, T., Torres, S., Hausser, I., Metze, D., Tursen, U., Lestringant, G.G., and Hennies, H.C. (2009). Ichthyosis, follicular atrophoderma, and hypotrichosis caused by mutations in ST14 is associated with impaired profilaggrin processing. J. Invest. Dermatol. 129, 862–869.10.1038/jid.2008.311Search in Google Scholar PubMed
Allen, A., Siegfried, E., Silverman, R., Williams, M.L., Elias, P.M., Szabo, S.K., and Korman, N.J. (2001). Significant absorption of topical tacrolimus in 3 patients with Netherton syndrome. Arch. Dermatol. 137, 747–750.Search in Google Scholar
Basel-Vanagaite, L., Attia, R., Ishida-Yamamoto, A., Rainshtein, L., Ben Amitai, D., Lurie, R., Pasmanik-Chor, M., Indelman, M., Zvulunov, A., Saban, S., et al., (2007). Autosomal recessive ichthyosis with hypotrichosis caused by a mutation in ST14, E., encoding type II transmembrane serine protease matriptase. Am. J. Hum. Genet. 80, 467–477.Search in Google Scholar
Beljan, G., Traupe, H., Metze D., and Sunderkotter, C. (2003). [Comel-Netherton syndrome with bacterial superinfection]. Hautarzt 54, 1198–1202.10.1007/s00105-003-0572-8Search in Google Scholar PubMed
Bennett, K., Callard, R., Heywood, W., Harper, J., Jayakumar, A., Clayman, G.L., Di, W.L., and Mills, K. (2010). New role for LEKTI in skin barrier formation: label-free quantitative proteomic identification of caspase 14 as a novel target for the protease inhibitor LEKTI. J. Proteome Res. 9, 4289–4294.10.1021/pr1003467Search in Google Scholar PubMed
Bennett, K., Heywood, W., Di, W.L., Harper, J., Clayman, G.L., Jayakumar, A., Callard R., and Mills, K. (2012). The identification of a new role for LEKTI in the skin: the use of protein ‘bait’ arrays to detect defective trafficking of dermcidin in the skin of patients with Netherton syndrome. J. Proteomics 75, 3925–3937.10.1016/j.jprot.2012.04.045Search in Google Scholar PubMed
Bens, G., Boralevi, F., Buzenet C., and Taieb, A. (2003). Topical treatment of Netherton’s syndrome with tacrolimus ointment without significant systemic absorption. Br. J. Dermatol. 149, 224–226.10.1046/j.1365-2133.2003.05443.xSearch in Google Scholar PubMed
Bitoun, E., Micheloni, A., Lamant, L., Bonnart, C., Tartaglia-Polcini, A., Cobbold, C., Al Saati, T., Mariotti, F., Mazereeuw-Hautier, J., Boralevi, F., et al., (2003). LEKTI proteolytic processing in human primary keratinocytes, M., tissue distribution and defective expression in Netherton syndrome. Hum. Mol. Genet. 12, 2417–2430.Search in Google Scholar
Bonnart, C., Deraison, C., Lacroix, M., Uchida, Y., Besson, C., Robin, A., Briot, A., Gonthier, M., Lamant, L., Dubus, P., et al. (2010). Elastase 2 is expressed in human and mouse epidermis and impairs skin barrier function in Netherton syndrome through filaggrin and lipid misprocessing. J. Clin. Invest. 120, 871–882.10.1172/JCI41440Search in Google Scholar PubMed PubMed Central
Borgoño, A.C., Michael, I.P., Komatsu, N., Jayakumar, A., Kapadia, R., Clayman, G.L., Sotiropoulou, G., and Diamandis, E.P. (2007). A potential role for multiple tissue kallikrein serine proteases in epidermal desquamation. J. Biol. Chem. 282, 3640–3652.10.1074/jbc.M607567200Search in Google Scholar PubMed
Brattsand, M., Stefansson, K., Lundh, C., Haasum, Y., and Egelrud, T. (2005). A proteolytic cascade of kallikreins in the stratum corneum. J. Invest. Dermatol. 124, 198–203.10.1111/j.0022-202X.2004.23547.xSearch in Google Scholar PubMed
Brattsand, M., Stefansson, K., Hubiche, T., Nilsson S.K., and Egelrud, T. (2009). SPINK9: a selective, skin-specific Kazal-type serine protease inhibitor. J. Invest. Dermatol. 129, 1656–1665.10.1038/jid.2008.448Search in Google Scholar PubMed
Briot, A., Deraison, C., Lacroix, M., Bonnart, C., Robin, A., Besson, C., Dubus, P., and Hovnanian, A. (2009). Kallikrein 5 induces atopic dermatitis-like lesions through PAR2-mediated thymic stromal lymphopoietin expression in Netherton syndrome. J. Exp. Med. 206, 1135–1147.10.1084/jem.20082242Search in Google Scholar PubMed PubMed Central
Briot, A., Lacroix, M., Robin, A., Steinhoff, M., Deraison, C., and Hovnanian, A. (2010). Par2 inactivation inhibits early production of TSLP, but not cutaneous inflammation, in Netherton syndrome adult mouse model. J. Invest. Dermatol. 130, 2736–2742.10.1038/jid.2010.233Search in Google Scholar PubMed
Buddenkotte, J., Stroh, C., Engels, I.H., Moormann, C., Shpacovitch, V.M., Seeliger, S., Vergnolle, N., Vestweber, D., Luger, T.A., Schulze-Osthoff, K., et al. (2005). Agonists of proteinase-activated receptor-2 stimulate upregulation of intercellular cell adhesion molecule-1 in primary human keratinocytes via activation of NF-κB. J. Invest. Dermatol. 124, 38–45.10.1111/j.0022-202X.2004.23539.xSearch in Google Scholar PubMed
Candi, E., Schmidt, R., and Melino, G. (2005). The cornified envelope: a model of cell death in the skin. Nat. Rev. Mol. Cell. Biol. 6, 328–340.10.1038/nrm1619Search in Google Scholar PubMed
Caubet, C., Jonca, N., Brattsand, M., Guerrin, M., Bernard, D., Schmidt, R., Egelrud, T., Simon, M., and Serre, G. (2004). Degradation of corneodesmosome proteins by two serine proteases of the kallikrein family, SCTE/KLK5/hK5 and SCCE/KLK7/hK7. J. Invest. Dermatol. 122, 1235–1244.10.1111/j.0022-202X.2004.22512.xSearch in Google Scholar PubMed
Chavanas, S., Bodemer, C., Rochat, A., Hamel-Teillac, D., Ali, M., Irvine, A.D., Bonafe, J.L., Wilkinson, J., Taieb, A., Barrandon, Y., et al., (2000). Mutations in SPINK5, encoding a serine protease inhibitor, cause Netherton syndrome. Nat. Genet. 25, 141–142.10.1038/75977Search in Google Scholar PubMed
Comel, M. (1949). Ichthyosis Linearis circumflexa. Dermatologica 98, 133–136.10.1159/000257290Search in Google Scholar
Dale, A.B., Resing, K.A., and Lonsdale-Eccles, J.D. (1985). Filaggrin: a keratin filament associated protein. Ann. NY Acad. Sci. 455, 330–342.10.1111/j.1749-6632.1985.tb50420.xSearch in Google Scholar PubMed
De, Y., Chen, Q., Schmidt, A.P., Anderson, G.M., Wang, J.M., Wooters, J., Oppenheim, J.J., and Chertov, O. (2000). LL-37, the neutrophil granule- and epithelial cell-derived cathelicidin, utilizes formyl peptide receptor-like 1 (FPRL1) as a receptor to chemoattract human peripheral blood neutrophils, monocytes, and T cells. J. Exp. Med. 192, 1069–1074.10.1084/jem.192.7.1069Search in Google Scholar PubMed PubMed Central
Denecker, G., Hoste, E., Gilbert, B., Hochepied, T., Ovaere, P., Lippens, S., Van den Broecke, C., Van Damme, P., D’Herde, K., Hachem, J.P., et al., (2007). Caspase-14 protects against epidermal UVB photodamage and water loss. Nat. Cell. Biol. 9, 666–674.10.1038/ncb1597Search in Google Scholar PubMed
Denecker, G., Ovaere, P., Vandenabeele, P., and Declercq, W. (2008). Caspase-14 reveals its secrets. J. Cell Biol. 180, 451–458.10.1083/jcb.200709098Search in Google Scholar PubMed PubMed Central
Deraison, C., Bonnart, C., Lopez, F., Besson, C., Robinson, R., Jayakumar, A., Wagberg, F., Brattsand, M., Hachem, J.P., Leonardsson, G., et al. (2007). LEKTI fragments specifically inhibit KLK5, KLK7, and KLK14 and control desquamation through a pH-dependent interaction. Mol. Biol. Cell 18, 3607–3619.10.1091/mbc.e07-02-0124Search in Google Scholar PubMed PubMed Central
Descargues, P., Deraison, C., Bonnart, C., Kreft, M., Kishibe, M., Ishida-Yamamoto, A., Elias, P., Barrandon, Y., Zambruno, G., Sonnenberg, A., et al., (2005). Spink5-deficient mice mimic Netherton syndrome through degradation of desmoglein 1 by epidermal protease hyperactivity. Nat. Genet. 37, 56–65.10.1038/ng1493Search in Google Scholar PubMed
Descargues, P., Deraison, C., Prost, C., Fraitag, S., Mazereeuw-Hautier, J., D’Alessio, M., Ishida-Yamamoto, A., Bodemer, C., Zambruno, G., and Hovnanian, A. (2006). Corneodesmosomal cadherins are preferential targets of stratum corneum trypsin- and chymotrypsin-like hyperactivity in Netherton syndrome. J. Invest. Dermatol. 126, 1622–1632.10.1038/sj.jid.5700284Search in Google Scholar PubMed
Di, L.W., Larcher, F., Semenova, E., Talbot, G.E., Harper, J.I., Del Rio, M., Thrasher, A.J., and Qasim, W. (2011). Ex-vivo gene therapy restores LEKTI activity and corrects the architecture of Netherton syndrome-derived skin grafts. Mol. Ther. 19, 408–416.10.1038/mt.2010.201Search in Google Scholar PubMed PubMed Central
Di, L.W., Mellerio, J.E., Bernadis, C., Harper, J., Abdul-Wahab, A., Ghani, S., Chan, L., Martinez-Queipo, M., Hara, H., McNicol, A.M., et al., (2013). Phase I study protocol for ex vivo lentiviral gene therapy for the inherited skin disease, Netherton syndrome. Hum. Gene. Ther. Clin. Dev. 24, 182–190.10.1089/humc.2013.195Search in Google Scholar PubMed
Egelrud, T., Brattsand, M., Kreutzmann, P., Walden, M., Vitzithum, K., Marx, U.C., Forssmann, W.G., and Magert, H.J. (2005). hK5 and hK7, two serine proteinases abundant in human skin, are inhibited by LEKTI domain 6. Br. J. Dermatol. 153, 1200–1203.10.1111/j.1365-2133.2005.06834.xSearch in Google Scholar PubMed
Eissa, A. and Diamandis, E.P. (2011). Kallikrein protease involvement in skin pathologies supports a new view of the origin of inflamed itchy skin. In: Proteases and Their Receptors in Inflammation. N. Vergnolle and M. Chignard, eds. (Basel, Switzerland: Springer), pp. 51–71.10.1007/978-3-0348-0157-7_3Search in Google Scholar
Elias, M.P., Hatano, Y., and Williams, M.L. (2008). Basis for the barrier abnormality in atopic dermatitis: outside-inside-outside pathogenic mechanisms. J. Allergy Clin. Immunol. 121, 1337–1343.10.1016/j.jaci.2008.01.022Search in Google Scholar PubMed PubMed Central
Fartasch, M., Williams, M.L., and Elias, P.M. (1999). Altered lamellar body secretion and stratum corneum membrane structure in Netherton syndrome: differentiation from other infantile erythrodermas and pathogenic implications. Arch. Dermatol. 135, 823–832.10.1001/archderm.135.7.823Search in Google Scholar PubMed
Folster-Holst, R., Swensson, O., Stockfleth, E., Monig, H., Mrowietz, U., and Christophers, E. (1999). Comel-Netherton syndrome complicated by papillomatous skin lesions containing human papillomaviruses 51 and 52 and plane warts containing human papillomavirus 16. Br. J. Dermatol. 140, 1139–1143.10.1046/j.1365-2133.1999.02892.xSearch in Google Scholar PubMed
Fontao, L., Laffitte, E., Briot, A., Kaya, G., Roux-Lombard, P., Fraitag, S., Hovnanian A.A., and Saurat, J.H. (2011). Infliximab infusions for netherton Syndrome: sustained clinical improvement correlates with a reduction of thymic stromal lymphopoietin levels in the skin. J. Invest. Dermatol. 131, 1947–1950.10.1038/jid.2011.124Search in Google Scholar PubMed
Fortugno, P., Bresciani, A., Paolini, C., Pazzagli, C., El Hachem, M., D’Alessio, M., and Zambruno, G. (2011). Proteolytic activation cascade of the Netherton syndrome-defective protein, LEKTI, in the epidermis: implications for skin homeostasis. J. Invest. Dermatol. 131, 2223–2232.10.1038/jid.2011.174Search in Google Scholar PubMed
Fuchs, E. and Raghavan, S. (2002). Getting under the skin of epidermal morphogenesis. Nat. Rev. Genet. 3, 199–209.10.1038/nrg758Search in Google Scholar PubMed
Furio, L. and Hovnanian, A. (2011). When activity requires breaking up: LEKTI proteolytic activation cascade for specific proteinase inhibition. J. Invest. Dermatol. 131, 2169–2173.10.1038/jid.2011.295Search in Google Scholar PubMed
Furio, L., de Veer, S., Jaillet, M., Briot, A., Robin, A., Deraison, C., and Hovnanian, A. (2014). Transgenic kallikrein 5 mice reproduce major cutaneous and systemic hallmarks of Netherton syndrome. J. Exp. Med. 211, 499–513.10.1084/jem.20131797Search in Google Scholar PubMed PubMed Central
Galliano, F.M., Toulza, E., Gallinaro, H., Jonca, N., Ishida-Yamamoto, A., Serre, G., and Guerrin, M. (2006). A novel protease inhibitor of the alpha2-macroglobulin family expressed in the human epidermis. J. Biol. Chem. 281, 5780–5789.10.1074/jbc.M508017200Search in Google Scholar PubMed
Giroux, D.J., Sizun, J., Gardach, C., Awad, H., Guillois, B., and Alix, D. (1993). Severe hypernatremic dehydration disclosing Netherton syndrome in the neonatal period. Arch. Fr. Pediatr. 50, 585–588.Search in Google Scholar
Godic, A. and Dragos, V. (2004). Successful treatment of Netherton’s syndrome with topical calcipotriol. Eur. J. Dermatol. 14, 115–117.Search in Google Scholar
Guma, M., Ronacher, L., Liu-Bryan, R., Takai, S., Karin, M., and Corr, M. (2009). Caspase 1-independent activation of interleukin-1beta in neutrophil-predominant inflammation. Arthritis Rheum. 60, 3642–3650.10.1002/art.24959Search in Google Scholar PubMed PubMed Central
Hachem, P.J., Wagberg, F., Schmuth, M., Crumrine, D., Lissens, W., Jayakumar, A., Houben, E., Mauro, T.M., Leonardsson, G., Brattsand, M., et al. (2006). Serine protease activity and residual LEKTI expression determine phenotype in Netherton syndrome. J. Invest. Dermatol. 126, 1609–1621.10.1038/sj.jid.5700288Search in Google Scholar PubMed
Hansson, L., Backman, A., Ny, A., Edlund, M., Ekholm, E., Ekstrand Hammarstrom, B., Tornell, J., Wallbrandt, P., Wennbo, H., and Egelrud, T. (2002). Epidermal overexpression of stratum corneum chymotryptic enzyme in mice: a model for chronic itchy dermatitis. J. Invest. Dermatol. 118, 444–449.10.1046/j.0022-202x.2001.01684.xSearch in Google Scholar PubMed
Hatano, Y., Terashi, H., Arakawa, S., and Katagiri, K. (2005). Interleukin-4 suppresses the enhancement of ceramide synthesis and cutaneous permeability barrier functions induced by tumor necrosis factor-alpha and interferon-gamma in human epidermis. J. Invest. Dermatol. 124, 786–792.10.1111/j.0022-202X.2005.23651.xSearch in Google Scholar PubMed
Hausser, I. and Anton-Lamprecht, I. (1996). Severe congenital generalized exfoliative erythroderma in newborns and infants: a possible sign of Netherton syndrome. Pediatr. Dermatol. 13, 183–199.10.1111/j.1525-1470.1996.tb01202.xSearch in Google Scholar PubMed
Heinz-Erian, P., Muller, T., Krabichler, B., Schranz, M., Becker, C., Ruschendorf, F., Nurnberg, P., Rossier, B., Vujic, M., Booth, I.W., et al., (2009). Mutations in SPINT2 cause a syndromic form of congenital sodium diarrhea. Am. J. Hum. Genet. 84, 188–196.10.1016/j.ajhg.2009.01.004Search in Google Scholar PubMed PubMed Central
Hewett, R.D., Simons, A.L., Mangan, N.E., Jolin, H.E., Green, S.M., Fallon, P.G., and McKenzie, A.N. (2005). Lethal, neonatal ichthyosis with increased proteolytic processing of filaggrin in a mouse model of Netherton syndrome. Hum. Mol. Genet. 14, 335–346.10.1093/hmg/ddi030Search in Google Scholar PubMed
Hintner, H., Jaschke, E., and Fritsch, P. (1980). Netherton syndrome: weakened immunity, generalized verrucosis and carcinogenesis. Hautarzt 31, 428–432.Search in Google Scholar
Hosomi, N., Fukai, K., Nakanishi, T., Funaki, S., and Ishii, M. (2008). Caspase-1 activity of stratum corneum and serum interleukin-18 level are increased in patients with Netherton syndrome. Br. J. Dermatol. 159, 744–746.10.1111/j.1365-2133.2008.08706.xSearch in Google Scholar PubMed
Hou, L., Kapas, S., Cruchley, A.T., Macey, M.G., Harriott, P., Chinni, C., Stone, S.R., and Howells, G.L. (1998). Immunolocalization of protease-activated receptor-2 in skin: receptor activation stimulates interleukin-8 secretion by keratinocytes in vitro. Immunology 94, 356–362.10.1046/j.1365-2567.1998.00528.xSearch in Google Scholar PubMed PubMed Central
Hovnanian, A. (2012). Netherton syndrome: new advances in clinic, disease mechanism and treatment. Expert Review 7, 81–92.10.1586/edm.11.85Search in Google Scholar
Hovnanian, A. (2013). Netherton syndrome: skin inflammation and allergy by loss of protease inhibition. Cell Tissue Res. 351, 289–300.10.1007/s00441-013-1558-1Search in Google Scholar PubMed
Ishida-Yamamoto, A., Deraison, C., Bonnart, C., Bitoun, E., Robinson, R., O’Brien, T.J., Wakamatsu, K., Ohtsubo, S., Takahashi, H., Hashimoto, Y., et al. (2005). LEKTI is localized in lamellar granules, separated from KLK5 and KLK7, and is secreted in the extracellular spaces of the superficial stratum granulosum. J. Invest. Dermatol. 124, 360–366.10.1111/j.0022-202X.2004.23583.xSearch in Google Scholar PubMed
Jayakumar, A., Kang, Y., Mitsudo, K., Henderson, Y., Frederick, M.J., Wang, M., El-Naggar, A.K., Marx, U.C., Briggs, K., and Clayman, G.L. (2004). Expression of LEKTI domains 6–9′ in the baculovirus expression system: recombinant LEKTI domains 6–9′ inhibit trypsin and subtilisin A. Protein Expr. Purif. 35, <softenter;93–101.10.1016/j.pep.2003.12.004Search in Google Scholar PubMed
Judge, R.M., Morgan, G., and Harper, J.I. (1994). A clinical and immunological study of Netherton’s syndrome. Br. J. Dermatol. 131, 615–621.10.1111/j.1365-2133.1994.tb04971.xSearch in Google Scholar PubMed
Komatsu, N., Saijoh, K., Toyama, T., Ohka, R., Otsuki, N., Hussack, G., Takehara, K., and Diamandis, E.P. (2005). Multiple tissue kallikrein mRNA and protein expression in normal skin and skin diseases. Br. J. Dermatol. 153, 274–281.10.1111/j.1365-2133.2005.06754.xSearch in Google Scholar PubMed
Komatsu, N., Saijoh, K., Otsuki, N., Kishi, T., Micheal, I.P., Obiezu, C.V., Borgono, C.A., Takehara, K., Jayakumar, A., Wu, H.K., et al., (2007). Proteolytic processing of human growth hormone by multiple tissue kallikreins and regulation by the serine protease inhibitor Kazal-Type5 (SPINK5) protein. Clin. Chim. Acta 377, 228–236.10.1016/j.cca.2006.10.009Search in Google Scholar PubMed
Krasagakis, K., Ioannidou, D.J., Stephanidou, M., Manios, A., Panayiotides, J.G., and Tosca, A.D. (2003). Early development of multiple epithelial neoplasms in Netherton syndrome. Dermatology 207, 182–184.10.1159/000071791Search in Google Scholar PubMed
Kreutzmann, P., Schulz, A., Standker, L., Forssmann, W.G., and Magert, H.J. (2004). Recombinant production, purification and biochemical characterization of domain 6 of LEKTI: a temporary Kazal-type-related serine proteinase inhibitor. J. Chromatogr. B. Analyt. Technol. Biomed. Life Sci. 803, 75–81.10.1016/j.jchromb.2003.07.016Search in Google Scholar PubMed
Leyvraz, C., Charles, R.P., Rubera, I., Guitard, M., Rotman, S., Breiden, B., Sandhoff, K., and Hummler, E. (2005). The epidermal barrier function is dependent on the serine protease CAP1/Prss8. J. Cell Biol. 170, 487–496.10.1083/jcb.200501038Search in Google Scholar PubMed PubMed Central
Li, L.A., Walsh, S., and McKay, D.R. (2011). Surgical management of a giant condyloma of Buschke-Lowenstein in a patient with Netherton syndrome using the pedicled anterolateral thigh flap–a case report. J. Plast. Reconstr. Aesthet. Surg. 64, 1533–1536.10.1016/j.bjps.2011.03.013Search in Google Scholar PubMed
List, K., Szabo, R., Wertz, P.W., Segre, J., Haudenschild, C.C., Kim, S.Y., and Bugge, T.H. (2003). Loss of proteolytically processed filaggrin caused by epidermal deletion of Matriptase/MT-SP1. J. Cell Biol. 163, 901–910.10.1083/jcb.200304161Search in Google Scholar PubMed PubMed Central
Matsui, T., Miyamoto, K., Kubo, A., Kawasaki, H., Ebihara, T., Hata, K., Tanahashi, S., Ichinose, S., Imoto, I., Inazawa, J., et al., (2011). SASPase regulates stratum corneum hydration through profilaggrin-to-filaggrin processing. EMBO Mol. Med. 3, 320–333.10.1002/emmm.201100140Search in Google Scholar PubMed PubMed Central
Mazereeuw-Hautier, J., Cope, J., Ong, C., Green, A., Hovnanian, A., and Harper, J.I. (2006). Topical recombinant alpha1-antitrypsin: a potential treatment for Netherton syndrome? Arch. Dermatol. 142, 396–398.10.1001/archderm.142.3.396Search in Google Scholar PubMed
Meyer-Hoffert, U., Wu, Z., and Schroder, J.M. (2009). Identification of lympho-epithelial Kazal-type inhibitor 2 in human skin as a kallikrein-related peptidase 5-specific protease inhibitor. PLoS One 4, e4372.10.1371/journal.pone.0004372Search in Google Scholar PubMed PubMed Central
Meyer-Hoffert, U., Wu, Z., Kantyka, T., Fischer, J., Latendorf, T., Hansmann, B., Bartels, J., He, Y., Glaser, R., and Schroder, J.M. (2010). Isolation of SPINK6 in human skin: selective inhibitor of kallikrein-related peptidases. J. Biol. Chem. 285, 32174–32181.10.1074/jbc.M109.091850Search in Google Scholar PubMed PubMed Central
Mitsudo, K., Jayakumar, A., Henderson, Y., Frederick, M.J., Kang, Y., Wang, M., El-Naggar, A.K., and Clayman, G.L. (2003). Inhibition of serine proteinases plasmin, trypsin, subtilisin A, cathepsin G, and elastase by LEKTI: a kinetic analysis. Biochemistry 42, 3874–3881.10.1021/bi027029vSearch in Google Scholar PubMed
Miyai, M., Matsumoto, Y., Yamanishi, H., Yamamoto-Tanaka, M., Tsuboi, R., and Hibino, T. (2014). Keratinocyte-Specific Mesotrypsin Contributes to the Desquamation Process via Kallikrein Activation and LEKTI Degradation. J Invest Dermatol. 134, 1665–1674.10.1038/jid.2014.3Search in Google Scholar PubMed
Mizutani, R.H., Schechter, N., Lazarus, G., Black, R.A., and Kupper, T.S. (1991). Rapid and specific conversion of precursor interleukin 1 beta (IL-1 beta) to an active IL-1 species by human mast cell chymase. J. Exp. Med. 174, 821–825.10.1084/jem.174.4.821Search in Google Scholar PubMed PubMed Central
Nagaike, K., Kawaguchi, M., Takeda, N., Fukushima, T., Sawaguchi, A., Kohama, K., Setoyama, M., and Kataoka, H. (2008). Defect of hepatocyte growth factor activator inhibitor type 1/serine protease inhibitor, Kunitz type 1 (Hai-1/Spint1) leads to ichthyosis-like condition and abnormal hair development in mice. Am. J. Pathol. 173, 1464–1475.10.2353/ajpath.2008.071142Search in Google Scholar PubMed PubMed Central
Natsuga, K., Akiyama, M., and Shimizu, H. (2011). Malignant skin tumours in patients with inherited ichthyosis. Br. J. Dermatol. 165, 263–268.10.1111/j.1365-2133.2011.10381.xSearch in Google Scholar PubMed
Netherton, E.W. (1958). A unique case of trichorrhexis nodosa: bamboo hairs. AMA Arch. Derm 78, 483–487.10.1001/archderm.1958.01560100059009Search in Google Scholar PubMed
Niyonsaba, F., Ushio, H., Hara, M., Yokoi, H., Tominaga, M., Takamori, K., Kajiwara, N., Saito, H., Nagaoka, I., Ogawa, H., et al., (2010). Antimicrobial peptides human beta-defensins and cathelicidin LL-37 induce the secretion of a pruritogenic cytokine IL-31 by human mast cells. J. Immunol. 184, 3526–3534.10.4049/jimmunol.0900712Search in Google Scholar PubMed
Ny, A. and Egelrud, T. (2003). Transgenic mice over-expressing a serine protease in the skin: evidence of interferon gamma-independent MHC II expression by epidermal keratinocytes. Acta Derm. Venereol. 83, 322–327.10.1080/00015550310003809Search in Google Scholar PubMed
Ny, A. and Egelrud, T. (2004). Epidermal hyperproliferation and decreased skin barrier function in mice overexpressing stratum corneum chymotryptic enzyme. Acta Derm. Venereol. 84, 18–22.10.1080/00015550310005924Search in Google Scholar PubMed
Nylander-Lundqvist, E. and 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.Search in Google Scholar
Ohler, A., Debela, M., Wagner, S., Magdolen, V., and Becker-Pauly, C. (2010). Analyzing the protease web in skin: meprin metalloproteases are activated specifically by KLK4, 5 and 8 vice versa leading to processing of proKLK7 thereby triggering its activation. Biol. Chem. 391, 455–460.10.1515/bc.2010.023Search in Google Scholar PubMed
Oji, V., Beljan, G., Beier, K., Traupe, H., and Luger, T.A. (2005). Topical pimecrolimus: a novel therapeutic option for Netherton syndrome. Br. J. Dermatol. 153, 1067–1068.10.1111/j.1365-2133.2005.06884.xSearch in Google Scholar PubMed
Ong, A. and Harper, J. (2006). Netherton’s syndrome. In: Textbook of Pediatric Dermatology. J. Harper, A. Oranje and N. Prose, eds. (Turin, Italy, Blackwell), pp. 1359–1366.Search in Google Scholar
Pearton, J.D., Nirunsuksiri, W., Rehemtulla, A., Lewis, S.P., Presland, R.B., and Dale, B.A. (2001). Proprotein convertase expression and localization in epidermis: evidence for multiple roles and substrates. Exp. Dermatol. 10, 193–203.10.1034/j.1600-0625.2001.010003193.xSearch in Google Scholar PubMed
Rattenholl, A. and Steinhoff, M. (2008). Proteinase-activated receptor-2 in the skin: receptor expression, activation and function during health and disease. Drug News Perspect. 21, 369–381.10.1358/dnp.2008.21.7.1255294Search in Google Scholar PubMed
Renner, D.E., Hartl, D., Rylaarsdam, S., Young, M.L., Monaco-Shawver, L., Kleiner, G., Markert, M.L., Stiehm, E.R., Belohradsky, B.H., Upton, M.P., et al. (2009). Comel-Netherton syndrome defined as primary immunodeficiency. J. Allergy Clin. Immunol. 124, 536–543.10.1016/j.jaci.2009.06.009Search in Google Scholar PubMed PubMed Central
Resing, A.K., Thulin, C., Whiting, K., al-Alawi, N., and Mostad, S. (1995). Characterization of profilaggrin endoproteinase 1. A regulated cytoplasmic endoproteinase of epidermis. J. Biol. Chem. 270, 28193–28198.10.1074/jbc.270.47.28193Search in Google Scholar PubMed
Roedl, D., Oji, V., Buters, J.T., Behrendt, H., and Braun-Falco, M. (2011). rAAV2-mediated restoration of LEKTI in LEKTI-deficient cells from Netherton patients. J. Dermatol. Sci. 61, 194–198.10.1016/j.jdermsci.2010.12.004Search in Google Scholar PubMed
Saghari, S., Woolery-Lloyd, H., and Nouri, K. (2002). Squamous cell carcinoma in a patient with Netherton’s syndrome. Inter. J. Dermatol. 41, 415–416.10.1046/j.1365-4362.2002.01444.xSearch in Google Scholar PubMed
Saif, H.G.B. and Al-Khenaizan, S. (2007). Netherton syndrome: successful use of topical tacrolimus and pimecrolimus in four siblings. Int. J. Dermatol. 46, 290–294.10.1111/j.1365-4632.2006.02956.xSearch in Google Scholar PubMed
Sakabe, J., Yamamoto, M., Hirakawa, S., Motoyama, A., Ohta, I., Tatsuno, K., Ito, T., Kabashima, K., Hibino, T., and Tokura, Y. (2013). Kallikrein-related peptidase 5 functions in proteolytic processing of profilaggrin in cultured human keratinocytes. J. Biol. Chem. 288, 17179–17189.10.1074/jbc.M113.476820Search in Google Scholar PubMed PubMed Central
Sales, U.K., Masedunskas, A., Bey, A.L., Rasmussen, A.L., Weigert, R., List, K., Szabo, R., Overbeek, P.A., and Bugge, T.H. (2010). Matriptase initiates activation of epidermal pro-kallikrein and disease onset in a mouse model of Netherton syndrome. Nat. Genet. 42, 676–683.10.1038/ng.629Search in Google Scholar PubMed PubMed Central
Sandilands, A., Sutherland, C., Irvine, A.D., and McLean, W.H. (2009). Filaggrin in the frontline: role in skin barrier function and disease. J. Cell Sci. 122, 1285–1294.10.1242/jcs.033969Search in Google Scholar PubMed PubMed Central
Schalkwijk, J., Chang, A., Janssen, P., De Jongh, G.J., and Mier, P.D. (1990). Skin-derived antileucoproteases (SKALPs): characterization of two new elastase inhibitors from psoriatic epidermis. Br. J. Dermatol. 122, 631–641.10.1111/j.1365-2133.1990.tb07285.xSearch in Google Scholar PubMed
Schechter, M.N., Choi, E.J., Wang, Z.M., Hanakawa, Y., Stanley, J.R., Kang, Y., Clayman, G.L. and Jayakumar, A. (2005). Inhibition of human kallikreins 5 and 7 by the serine protease inhibitor lympho-epithelial Kazal-type inhibitor (LEKTI). Biol. Chem. 386, 1173–1184.10.1515/BC.2005.134Search in Google Scholar PubMed
Segre, J.A. (2006). Epidermal barrier formation and recovery in skin disorders. J. Clin. Invest. 116, 1150–1158.10.1172/JCI28521Search in Google Scholar PubMed PubMed Central
Soumelis, V., Reche, P.A., Kanzler, H., Yuan, W., Edward, G., Homey, B., Gilliet, M., Ho, S., Antonenko, S., Lauerma, A., et al. (2002). Human epithelial cells trigger dendritic cell mediated allergic inflammation by producing TSLP. Nat. Immunol. 3, 673–680.10.1038/ni805Search in Google Scholar PubMed
Stehlik, C. (2009). Multiple interleukin-1beta-converting enzymes contribute to inflammatory arthritis. Arthritis Rheum. 60, 3524–3530.10.1002/art.24961Search in Google Scholar PubMed PubMed Central
Steinhoff, M., Corvera, C.U., Thoma, M.S., Kong, W., McAlpine, B.E., Caughey, G.H., Ansel, J.C., and Bunnett, N.W. (1999). Proteinase-activated receptor-2 in human skin: tissue distribution and activation of keratinocytes by mast cell tryptase. Exp. Dermatol. 8, 282–294.10.1111/j.1600-0625.1999.tb00383.xSearch in Google Scholar PubMed
Steinhoff, M., Neisius, U., Ikoma, A., Fartasch, M., Heyer, G., Skov, P.S., Luger, T.A., and Schmelz M. (2003). Proteinase- activated receptor-2 mediates itch: a novel pathway for pruritus in human skin. J. Neurosci. 23, 6176–6180.10.1523/JNEUROSCI.23-15-06176.2003Search in Google Scholar
Stoll, C., Alembik, Y., Tchomakov, D., Messer, J., Heid, E., Boehm, N., Calvas, P., and Hovnanian, A. (2001). Severe hypernatremic dehydration in an infant with Netherton syndrome. Genet. Couns. 12, 237–243.Search in Google Scholar
Stryk, S., Siegfried, E.C., and Knutsen, A.P. (1999). Selective antibody deficiency to bacterial polysaccharide antigens in patients with Netherton syndrome. Pediatr. Dermatol. 16, 19–22.10.1046/j.1525-1470.1999.99005.xSearch in Google Scholar PubMed
Sun, J.D. and Linden, K.G. (2006). Netherton syndrome: a case report and review of the literature. Int J Dermatol. 45, 693–697.10.1111/j.1365-4632.2005.02637.xSearch in Google Scholar PubMed
Szabo, R., Kosa, P., List, K., and Bugge, T.H. (2009). Loss of matriptase suppression underlies spint1 mutation-associated ichthyosis and postnatal lethality. Am. J. Pathol. 174, 2015–2022.10.2353/ajpath.2009.090053Search in Google Scholar PubMed PubMed Central
Takai, T. and Ikeda, S. (2011). Barrier dysfunction caused by environmental proteases in the pathogenesis of allergic diseases. Allergol. Int. 60, 25–35.10.2332/allergolint.10-RAI-0273Search in Google Scholar PubMed
Tartaglia-Polcini, A., Bonnart, C., Micheloni, A., Cianfarani, F., Andre, A., Zambruno, G., Hovnanian, A., and D’Alessio, M. (2006). SPINK5, the defective gene in netherton syndrome, encodes multiple LEKTI isoforms derived from alternative pre-mRNA processing. J. Invest. Dermatol. 126, 315–324.10.1038/sj.jid.5700015Search in Google Scholar PubMed
Traupe, H. (1989). The Comel-Netherton syndrome. The Ichthyoses. A Guide to Clinical Diagnosis, Genetic Counseling and Therapy. (Berlin, Germany: Springer-Verlag), pp. 168–178.10.1007/978-3-642-73650-6_17Search in Google Scholar
van der Voort, E.A. and Prens, E.P. (2013). Netherton syndrome with multiple non-melanoma skin cancers. Acta Derm. Venereol. 93, 727–728.10.2340/00015555-1558Search in Google Scholar PubMed
Van Gysel, D., Koning, H., Baert, M.R., Savelkoul, H.F., Neijens, H.J., and Oranje, A.P. (2001). Clinico-immunological heterogeneity in Comel-Netherton syndrome. Dermatology 202, 99–107.10.1159/000051607Search in Google Scholar PubMed
Wakita, H., Furukawa, F., and Takigawa, M. (1997). Thrombin and trypsin induce granulocyte-macrophage colony-stimulating factor and interleukin-6 gene expression in cultured normal human keratinocytes. Proc. Assoc. Am. Physicians 109, 190–207.Search in Google Scholar
Weber, F., Fuchs, P.G., Pfister, H.J., Hinter, H., Fritsch, P., and Hoepfl, R. (2001). Human papillomavirus infection in Nehterton’s syndrome. Br. J. Dermatol. 144, 1044–1049.10.1046/j.1365-2133.2001.04196.xSearch in Google Scholar PubMed
Wingens, P.M., van Bergen, B.H., Hiemstra, P.S., Meis, J.F., van Vlijmen-Willems, I.M., Zeeuwen, P.L., Mulder, J., Kramps, H.A., van Ruissen, F., and Schalkwijk, J. (1998). Induction of SLPI (ALP/HUSI-I) in epidermal keratinocytes. J. Invest. Dermatol. 111, 996–1002.10.1046/j.1523-1747.1998.00425.xSearch in Google Scholar PubMed
Witt, H., Luck, W., Hennies, H.C., Classen, M., Kage, A., Lass, U., Landt, O., and Becker, M. (2000). Mutations in the gene encoding the serine protease inhibitor Kazal type 1 are associated with chronic pancreatitis. Nat. Genet. 25, 213–216.10.1038/76088Search in Google Scholar PubMed
Yamasaki, K., Schauber, J., Coda, A., Lin, H., Dorschner, R.A., Schechter, N.M., Bonnart, C., Descargues, P., Hovnanian, A., and Gallo, R.L. (2006). Kallikrein-mediated proteolysis regulates the antimicrobial effects of cathelicidins in skin. Faseb J. 20, 2068–2080.10.1096/fj.06-6075comSearch in Google Scholar PubMed
Yamasaki, K., Kanada, K., Macleod, D.T., Borkowski, A.W., Morizane, S., Nakatsuji, T., Cogen, A.L., and Gallo, R.L. (2011). TLR2 expression is increased in rosacea and stimulates enhanced serine protease production by keratinocytes. J. Invest. Dermatol. 131, 688–697.10.1038/jid.2010.351Search in Google Scholar PubMed PubMed Central
Yamazaki, M., Ishidoh, K., Suga, Y., Saido, T.C., Kawashima, S., Suzuki, K., Kominami, E., and Ogawa, H. (1997). Cytoplasmic processing of human profilaggrin by active mu-calpain. Biochem. Biophys. Res. Commun. 235, 652–656.10.1006/bbrc.1997.6809Search in Google Scholar PubMed
Yan, C, A., Honig, P.J., Ming, M.E., Weber, J., and Shah, K.N. (2010). The safety and efficacy of pimecrolimus 1% cream for the treatment of Netherton syndrome: results from an exploratory study. Arch. Dermatol. 146, 57–62.10.1001/archdermatol.2009.326Search in Google Scholar PubMed
Yang, T., Liang, D., Koch, P.J., Hohl, D., Kheradmand, F., and Overbeek, P.A. (2004). Epidermal detachment, desmosomal dissociation, and destabilization of corneodesmosin in Spink5-/- mice. Genes Dev. 18, 2354–2358.10.1101/gad.1232104Search in Google Scholar PubMed PubMed Central
Yousef, M, G., Bharaj, B.S., Yu, H., Poulopoulos, J., and Diamandis, E.P. (2001). Sequence analysis of the human kallikrein gene locus identifies a unique polymorphic minisatellite element. Biochem. Biophys. Res. Commun. 285, 1321–1329.10.1006/bbrc.2001.5321Search in Google Scholar PubMed
©2014 by De Gruyter