Friend or Foe? – Psoriasin und Koebnerisin

Zusammenfassung

Psoriasin (S100A7) und Koebnerisin (S100A15) wurden zuerst in entzündeter Haut von Psoriasispatienten entdeckt. Durch Genduplikationen im Epidermalen Differenzierungskomplex (Chromosom 1q21) sind beide entstanden und bilden eine eigene S100 Unterfamilie beim Menschen. Trotz ihrer hohen Homologie (> 90 % Sequenzgleichheit) weisen Psoriasin und Koebnerisin Unterschiede in ihrer Verteilung im Gewebe auf, ihrer Regulation und Funktion. Beide Proteine wirken multifunktionell als antimikrobielle Peptide (AMPs), initiieren und fördern synergistisch Entzündungsreaktionen als endogene Gefahrensignale („Alarmine“) und Chemoattraktoren und fördern zusammen die Zellmigration. Aufgrund ihrer unterschiedlichen Eigenschaften ist es zwingend notwendig, Psoriasin und Koebnerisin in der epithelialen Homöostase, bei Entzündungen und Tumorigenese zu unterscheiden.

Abstract

Psoriasin (S100A7) and koebnerisin (S100A15) were first identified in inflamed psoriatic skin. They have lately evolved by gene duplications within the Epidermal Differentiation Complex (chromosome 1q21) and form a novel S100 subfamily in human. Despite highest homology (> 90 %), psoriasin and koebnerisin are distinct in tissue distribution, regulation, and function. They act differently as antimicrobial peptides (AMP) and synergize to promote inflammation and cell migration as endogenous danger signals („alarmines“) and chemoattractants. Their different properties are compelling reasons to discriminate psoriasin and koebnerisin in epithelial homeostasis, inflammation and epithelial carcinogenesis.

Schlüsselwörter

antimikrobielle Peptide - Chemokine - Erkrankungsneigung - Orthologe

Keywords

antimicrobial peptides - chemoattractants - disease susceptibility - orthologs

• Literatur

• 1 Eckert RL, Broome AM, Ruse M et al. S100 proteins in the epidermis. J Invest Dermatol 2004; 123: 23-33
• 2 Emberley ED, Niu Y, Njue C et al. Psoriasin (S100A7) expression is associated with poor outcome in estrogen receptor-negative invasive breast cancer. Clin Cancer Res 2003; 9: 2627-2631
• 3 Gläser R, Harder J, Lange H et al. Antimicrobial psoriasin (S100A7) protects human skin from Escherichia coli infection. Nat Immunol 2005; 6: 57-64
• 4 Heizmann CW, Fritz G, Schäfer BW. S100 proteins: structure, functions and pathology. Front Biosci 2002; 7: d1356-1368
• 5 Lowes MA, Bowcock AM, Krueger JG. Pathogenesis and therapy of psoriasis. Nature 2007; 445: 866-873
• 6 Madsen P, Rasmussen HH, Leffers H et al. Molecular cloning, occurrence, and expression of a novel partially secreted protein "psoriasin" that is highly up-regulated in psoriatic skin. J Invest Dermatol 1991; 97: 701-712
• 7 Mischke D, Korge BP, Marenholz I et al. Genes encoding structural proteins of epidermal cornification and S100 calcium-binding proteins form a gene complex ("epidermal differentiation complex") on human chromosome 1q21. J Invest Dermatol 1996; 106: 989-992
• 8 Moog-Lutz C, Bouillet P, Regnier CH et al. Comparative expression of the psoriasin (S100A7) and S100C genes in breast carcinoma and co-localization to human chromosome 1q21-q22. Int J Cancer 1995; 63: 297-303
• 9 Moore BW. A soluble protein characteristic of the nervous system. Biochem Biophys Res Commun 1965; 19: 739-744
• 10 Schröder JM, Harder J. Antimicrobial skin peptides and proteins. Cell Mol Life Sci 2006; 63: 469-486
• 11 Wolf R, Howard OM, Dong HF et al. Chemotactic activity of S100A7 (Psoriasin) is mediated by the receptor for advanced glycation end products and potentiates inflammation with highly homologous but functionally distinct S100A15. J Immunol 2008; 181: 1499-1506
• 12 Wolf R, Mascia F, Dharamsi A et al. Gene from a psoriasis susceptibility locus primes the skin for inflammation. Sci Transl Med 2010; a 2: 61ra90
• 13 Wolf R, Mirmohammadsadegh A, Walz M et al. Molecular cloning and characterization of alternatively spliced mRNA isoforms from psoriatic skin encoding a novel member of the S100 family. FASEB J 2003; 17: 1969-1971
• 14 Wolf R, Ruzicka T, Yuspa SH. Novel S100A7 (psoriasin)/S100A15 (koebnerisin) subfamily: highly homologous but distinct in regulation and function. Amino Acids 2010; b 41: 789-796
• 15 Wolf R, Voscopoulos C, Winston J et al. Highly homologous hS100A15 and hS100A7 proteins are distinctly expressed in normal breast tissue and breast cancer. Cancer Lett 2009; 277: 101-107
• 16 Zhang XJ, Huang W, Yang S et al. Psoriasis genome-wide association study identifies susceptibility variants within LCE gene cluster at 1q21. Nat Genet 2009; 41: 205-210