Higher Expression of Lympho-epithelial Kazal-type-Related Inhibitor-1 Fragments and Decreased Desquamation in the Lesional Skin of Nummular Eczema

Authors

  • Sara Estefania Montenegro Department of Dermatology, Seoul National University College of Medicine, Seoul, Republic of Korea; Institute of Human‐Environment Interface Biology, Medical Research Center, Seoul National University, Seoul, Republic of Korea; Laboratory of Cutaneous Aging Research, Biomedical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea
  • Jang-Hee Oh Department of Dermatology, Seoul National University College of Medicine, Seoul, Republic of Korea; Institute of Human‐Environment Interface Biology, Medical Research Center, Seoul National University, Seoul, Republic of Korea; Laboratory of Cutaneous Aging Research, Biomedical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea
  • Joong Heon Suh Department of Dermatology, Seoul National University College of Medicine, Seoul, Republic of Korea; Institute of Human‐Environment Interface Biology, Medical Research Center, Seoul National University, Seoul, Republic of Korea; Laboratory of Cutaneous Aging Research, Biomedical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea
  • Je-Ho Mun Department of Dermatology, Seoul National University College of Medicine, Seoul, Republic of Korea; Institute of Human‐Environment Interface Biology, Medical Research Center, Seoul National University, Seoul, Republic of Korea; Laboratory of Cutaneous Aging Research, Biomedical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea
  • Jin Ho Chung Department of Dermatology, Seoul National University College of Medicine, Seoul, Republic of Korea; Institute of Human‐Environment Interface Biology, Medical Research Center, Seoul National University, Seoul, Republic of Korea; Laboratory of Cutaneous Aging Research, Biomedical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea; Institute on Aging, Seoul National University, Seoul, Republic of Korea

DOI:

https://doi.org/10.2340/actadv.v104.18636

Keywords:

Corneodesmosin, Desmocollin-1, Desmoglein-1, Lympho-epithelial Kazal-type-related inhibitor, Nummular eczema

Abstract

Nummular eczema, a chronic dermatitis characterized by coin-shaped lesions, was first documented in 1857. However, its pathophysiological characteristics are still not well known. To investigate differences in the regulation of the desquamation process in the stratum corneum of lesional and nonlesional skin of patients with nummular eczema and healthy control subjects, tape-stripped stratum corneum samples from patients with nummular eczema and healthy volunteers were analysed using immunofluorescence staining and western blot analysis. In the nummular eczema lesional skin, expression of desmoglein-1, desmocollin-1, and corneodesmosin exhibited a disorganized, dense or partially diffuse non-peripheral pattern with increased intensity, compared with the peripheral patterns observed in healthy or nonlesional skin, suggesting the impaired desquamation process in nummular eczema. Furthermore, although the expression of the desquamation-related serine proteases, kallikrein-related peptidase 7 and 5, was increased in nummular eczema lesional skin, the immunofluorescence staining of lympho-epithelial Kazal-type-related inhibitor-1, an endogenous inhibitor of various kallikrein-related peptidases, and its fragments were significantly increased in the nummular eczema lesional skin, suggesting its contribution to the inhibition of corneodesmosomal degradation. Therefore, the increased detection of corneodesmosomal proteins in nummular eczema lesions may be due to the increased amount of the fragments of lympho-epithelial Kazal-type-related inhibitor-1, which could contribute to delayed desquamation.

Downloads

Download data is not yet available.

References

Bonamonte D, Foti C, Vestita M, Ranieri LD, Angelini G. Nummular eczema and contact allergy: a retrospective study. Dermatitis 2012; 23: 153-157.

https://doi.org/10.1097/DER.0b013e318260d5a0 DOI: https://doi.org/10.1097/DER.0b013e318260d5a0

Reich D, Psomadakis CE, Buka B. Nummular wczema. In: Reich D, Psomadakis CE, Buka B, editors. Top 50 dermatology case studies for primary care. Cham: Springer International Publishing; 2017: p. 167-172.

https://doi.org/10.1007/978-3-319-18627-6_27 DOI: https://doi.org/10.1007/978-3-319-18627-6_27

Halberg M. Nummular eczema. J Emerg Med 2012; 43: e327-328.

https://doi.org/10.1016/j.jemermed.2011.05.031 DOI: https://doi.org/10.1016/j.jemermed.2011.05.031

Lugovic-Mihic L, Bukvic I, Bulat V, Japundzic I. Factors contributing to chronic urticaria/angioedema and nummular eczema resolution: which findings are crucial? Acta Clin Croat 2019; 58: 595-603.

https://doi.org/10.20471/acc.2019.58.04.05 DOI: https://doi.org/10.20471/acc.2019.58.04.05

Krogh HK. Nummular eczema. Its relationship to internal foci of infection. A survey of 84 case records. Acta Derm Venereol 1960; 40: 114-126.

Tanaka T, Satoh T, Yokozeki H. Dental infection associated with nummular eczema as an overlooked focal infection. J Dermatol 2009; 36: 462-465.

https://doi.org/10.1111/j.1346-8138.2009.00677.x DOI: https://doi.org/10.1111/j.1346-8138.2009.00677.x

Aoyama H, Tanaka M, Hara M, Tabata N, Tagami H. Nummular eczema: an addition of senile xerosis and unique cutaneous reactivities to environmental aeroallergens. Dermatology 1999; 199: 135-139.

https://doi.org/10.1159/000018220 DOI: https://doi.org/10.1159/000018220

Higgins EM, du Vivier AW. Cutaneous disease and alcohol misuse. Br Med Bull 1994; 50: 85-98.

https://doi.org/10.1093/oxfordjournals.bmb.a072887 DOI: https://doi.org/10.1093/oxfordjournals.bmb.a072887

Jiamton S, Tangjaturonrusamee C, Kulthanan K. Clinical features and aggravating factors in nummular eczema in Thais. Asian Pac J Allergy Immunol 2013; 31: 36-42.

Meyer-Hoffert U. Reddish, scaly, and itchy: how proteases and their inhibitors contribute to inflammatory skin diseases. Arch Immunol Ther Exp (Warsz) 2009; 57: 345-354.

https://doi.org/10.1007/s00005-009-0045-6 DOI: https://doi.org/10.1007/s00005-009-0045-6

Nemeth V, Evans J. Eczema. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan. [cited 2022 Aug 8] Available from: https://www.ncbi.nlm.nih.gov/books/NBK538209/

Simon M, Bernard D, Minondo AM, Camus C, Fiat F, Corcuff P, et al. Persistence of both peripheral and non-peripheral corneodesmosomes in the upper stratum corneum of winter xerosis skin versus only peripheral in normal skin. J Invest Dermatol 2001; 116: 23-30.

https://doi.org/10.1046/j.1523-1747.2001.00208.x DOI: https://doi.org/10.1046/j.1523-1747.2001.00208.x

Igawa S, Kishibe M, Minami-Hori M, Honma M, Tsujimura H, Ishikawa J, et al. Incomplete KLK7 secretion and upregulated LEKTI expression underlie hyperkeratotic stratum corneum in atopic dermatitis. J Invest Dermatol 2017; 137: 449-456.

https://doi.org/10.1016/j.jid.2016.10.015 DOI: https://doi.org/10.1016/j.jid.2016.10.015

Delattre C, Winstall E, Lessard C, Donovan M, Simonetti L, Minondo AM, et al. Proteomic analysis identifies new biomarkers for postmenopausal and dry skin. Exp Dermatol 2012; 21: 205-210.

https://doi.org/10.1111/j.1600-0625.2011.01434.x DOI: https://doi.org/10.1111/j.1600-0625.2011.01434.x

Haftek M. Epidermal barrier disorders and corneodesmosome defects. Cell Tissue Res 2015; 360: 483-490.

https://doi.org/10.1007/s00441-014-2019-1 DOI: https://doi.org/10.1007/s00441-014-2019-1

Whittock NV, Bower C. Targetting of desmoglein 1 in inherited and acquired skin diseases. Clin Exp Dermatol 2003; 28: 410-415.

https://doi.org/10.1046/j.1365-2230.2003.01311.x DOI: https://doi.org/10.1046/j.1365-2230.2003.01311.x

Kitajima Y. Regulation and impairments of dynamic desmosome and corneodesmosome remodeling. Eur J Dermatol 2013; 10.1684/ejd.2013.1976.

Simon M, Jonca N, Guerrin M, Haftek M, Bernard D, Caubet C, et al. Refined characterization of corneodesmosin proteolysis during terminal differentiation of human epidermis and its relationship to desquamation. J Biol Chem 2001; 276: 20292-20299.

https://doi.org/10.1074/jbc.M100201200 DOI: https://doi.org/10.1074/jbc.M100201200

Simon M, Montezin M, Guerrin M, Durieux JJ, Serre G. Characterization and purification of human corneodesmosin, an epidermal basic glycoprotein associated with corneocyte-specific modified desmosomes. J Biol Chem 1997; 272: 31770-31776.

https://doi.org/10.1074/jbc.272.50.31770 DOI: https://doi.org/10.1074/jbc.272.50.31770

Richters RJH, Uzunbajakava NE, Timofeeva N, van de Kerkhof PCM, van Erp PEJ. Development of a novel approach to studying corneodesmosomes and stratum corneum adhesion: extending knowledge on the pathophysiology of sensitive skin. Skin Pharmacol Physiol 2019; 32: 81-93.

https://doi.org/10.1159/000495070 DOI: https://doi.org/10.1159/000495070

Matsui T, Amagai M. Dissecting the formation, structure and barrier function of the stratum corneum. Int Immunol 2015; 27: 269-280.

https://doi.org/10.1093/intimm/dxv013 DOI: https://doi.org/10.1093/intimm/dxv013

Fernandez IS, Standker L, Magert HJ, Forssmann WG, Gimenez-Gallego G, Romero A. Crystal structure of human epidermal kallikrein 7 (hK7) synthesized directly in its native state in E. coli: insights into the atomic basis of its inhibition by LEKTI domain 6 (LD6). J Mol Biol 2008; 377: 1488-1497.

https://doi.org/10.1016/j.jmb.2008.01.089 DOI: https://doi.org/10.1016/j.jmb.2008.01.089

Caubet C, Jonca N, Brattsand M, Guerrin M, Bernard D, Schmidt R, et al. Degradation of corneodesmosome proteins by two serine proteases of the kallikrein family, SCTE/KLK5/hK5 and SCCE/KLK7/hK7. J Invest Dermatol 2004; 122: 1235-1244.

https://doi.org/10.1111/j.0022-202X.2004.22512.x DOI: https://doi.org/10.1111/j.0022-202X.2004.22512.x

Borgono CA, Michael IP, Komatsu N, Jayakumar A, Kapadia R, Clayman GL, et al. A potential role for multiple tissue kallikrein serine proteases in epidermal desquamation. J Biol Chem 2007; 282: 3640-3652.

https://doi.org/10.1074/jbc.M607567200 DOI: https://doi.org/10.1074/jbc.M607567200

Ishida-Yamamoto A, Igawa S, Kishibe M, Honma M. Clinical and molecular implications of structural changes to desmosomes and corneodesmosomes. J Dermatol 2018; 45: 385-389.

https://doi.org/10.1111/1346-8138.14202 DOI: https://doi.org/10.1111/1346-8138.14202

Deraison C, Bonnart C, Lopez F, Besson C, Robinson R, Jayakumar A, et al. LEKTI fragments specifically inhibit KLK5, KLK7, and KLK14 and control desquamation through a pH-dependent interaction. Mol Biol Cell 2007; 18: 3607-3619.

https://doi.org/10.1091/mbc.e07-02-0124 DOI: https://doi.org/10.1091/mbc.e07-02-0124

Bennett K, Callard R, Heywood W, Harper J, Jayakumar A, Clayman GL, et al. 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 2010; 9: 4289-4294.

https://doi.org/10.1021/pr1003467 DOI: https://doi.org/10.1021/pr1003467

Hanifin JM, Baghoomian W, Grinich E, Leshem YA, Jacobson M, Simpson EL. The eczema area and severity index: a practical guide. Dermatitis 2022; 33: 187-192.

https://doi.org/10.1097/DER.0000000000000895 DOI: https://doi.org/10.1097/DER.0000000000000895

Lin TK, Crumrine D, Ackerman LD, Santiago JL, Roelandt T, Uchida Y, et al. Cellular changes that accompany shedding of human corneocytes. J Invest Dermatol 2012; 132: 2430-2439.

https://doi.org/10.1038/jid.2012.173 DOI: https://doi.org/10.1038/jid.2012.173

Iwatsuki K, Harada H, Yokote R, Kaneko F. Differences in the expression of pemphigus antigens during epidermal differentiation. Br J Dermatol 1995; 133: 209-216.

https://doi.org/10.1111/j.1365-2133.1995.tb02617.x DOI: https://doi.org/10.1111/j.1365-2133.1995.tb02617.x

Delva E, Tucker DK, Kowalczyk AP. The desmosome. Cold Spring Harb Perspect Biol 2009; 1: a002543.

https://doi.org/10.1101/cshperspect.a002543 DOI: https://doi.org/10.1101/cshperspect.a002543

Kopp T, Sitaru C, Pieczkowski F, Schneeberger A, Fodinger D, Zillikens D, et al. IgA pemphigus: occurrence of anti-desmocollin 1 and anti-desmoglein 1 antibody reactivity in an individual patient. J Dtsch Dermatol Ges 2006; 4: 1045-1050.

https://doi.org/10.1111/j.1610-0387.2006.06166.x DOI: https://doi.org/10.1111/j.1610-0387.2006.06166.x

Tartaglia-Polcini A, Bonnart C, Micheloni A, Cianfarani F, Andre A, Zambruno G, et al. SPINK5, the defective gene in netherton syndrome, encodes multiple LEKTI isoforms derived from alternative pre-mRNA processing. J Invest Dermatol 2006; 126: 315-324.

https://doi.org/10.1038/sj.jid.5700015 DOI: https://doi.org/10.1038/sj.jid.5700015

Fortugno P, Bresciani A, Paolini C, Pazzagli C, El Hachem M, D'Alessio M, et al. Proteolytic activation cascade of the Netherton syndrome-defective protein, LEKTI, in the epidermis: implications for skin homeostasis. J Invest Dermatol 2011; 131: 2223-2232.

https://doi.org/10.1038/jid.2011.174 DOI: https://doi.org/10.1038/jid.2011.174

Chavarria-Smith J, Chiu CPC, Jackman JK, Yin J, Zhang J, Hackney JA, et al. Dual antibody inhibition of KLK5 and KLK7 for Netherton syndrome and atopic dermatitis. Sci Transl Med 2022; 14: eabp9159.

https://doi.org/10.1126/scitranslmed.abp9159 DOI: https://doi.org/10.1126/scitranslmed.abp9159

Komatsu N, Saijoh K, Kuk C, Liu AC, Khan S, Shirasaki F, et al. Human tissue kallikrein expression in the stratum corneum and serum of atopic dermatitis patients. Exp Dermatol 2007; 16: 513-519.

https://doi.org/10.1111/j.1600-0625.2007.00562.x DOI: https://doi.org/10.1111/j.1600-0625.2007.00562.x

Bitoun E, Micheloni A, Lamant L, Bonnart C, Tartaglia-Polcini A, Cobbold C, et al. LEKTI proteolytic processing in human primary keratinocytes, tissue distribution and defective expression in Netherton syndrome. Hum Mol Genet 2003; 12: 2417-2430.

https://doi.org/10.1093/hmg/ddg247 DOI: https://doi.org/10.1093/hmg/ddg247

Sugihara S, Sugimoto S, Tachibana K, Kobashi M, Nomura H, Miyake T, et al. TNF-alpha and IL-17A induce the expression of lympho-epithelial Kazal-type inhibitor in epidermal keratinocytes. J Dermatol Sci 2019; 96: 26-32.

https://doi.org/10.1016/j.jdermsci.2019.08.007 DOI: https://doi.org/10.1016/j.jdermsci.2019.08.007

Sugimoto S, Morizane S, Nomura H, Kobashi M, Sugihara S, Iwatsuki K. Toll-like receptor signaling induces the expression of lympho-epithelial Kazal-type inhibitor in epidermal keratinocytes. J Dermatol Sci 2018; 92: 181-187.

https://doi.org/10.1016/j.jdermsci.2018.09.001 DOI: https://doi.org/10.1016/j.jdermsci.2018.09.001

Bohner A, Jargosch M, Muller NS, Garzorz-Stark N, Pilz C, Lauffer F, et al. The neglected twin: nummular eczema is a variant of atopic dermatitis with codominant T(H)2/T(H)17 immune response. J Allergy Clin Immunol 2023; 152: 408-419.

https://doi.org/10.1016/j.jaci.2023.04.009 DOI: https://doi.org/10.1016/j.jaci.2023.04.009

Published

2024-03-29

How to Cite

Montenegro, S. E., Oh, J.-H., Suh, J. H., Mun, J.-H., & Chung, J. H. (2024). Higher Expression of Lympho-epithelial Kazal-type-Related Inhibitor-1 Fragments and Decreased Desquamation in the Lesional Skin of Nummular Eczema. Acta Dermato-Venereologica, 104, adv188636. https://doi.org/10.2340/actadv.v104.18636