İnflamasyonun Önemli Bir Düzenleyicisi Olarak S100 Proteinleri

Year 2020, Volume: 53 Issue: Ek Sayı 1, 41 - 45, 30.06.2020

Emrah Salman Reyhan Bilici Salman Abdurrahman Tufan

https://doi.org/10.20492/aeahtd.680724

Cited By: 2

Abstract

S100 proteinleri amonyum sülfatta %100 çözünürlükleri olan, kalsiyum bağlayan, küçük (10-12 kDa) asidik sitozolik proteinlerdir. Kalsiyum bağlanmasıyla S100 proteinleri konformasyonel değişikliğe uğrar ve spesifik ligand veya reseptörlerine bağlanır ayrıca S100 proteinlerinin hemen hepsi homodimer ve/veya heterodimer formasyonu göstermektedir. S100 proteinleri hücre proliferasyonu, protein fosforilasyonu, farklılaşma, enerji metabolizması, kalsiyum homeostazı, inflamasyon ve hücre ölümü gibi çeşitli süreçlerde görev almaktadır.S100 proteinlerinin ekpresyonu kardiyomiyopatiler, Alzheimer gibi santral sinir sitemi hastalıkları, kanser ve inflamatuvar hastalıklarda değişmektedir.S100 A4 erken kanser teşhisi ve kanser metastazını öngörmede umut vadeden bir belirteçtir. Hiperproliferatif ve inflamatuvar cilt hastalıklarında S100A7 ekspresyonunda artış görülür ve bu değişken ekspresyon epitelyal cilt kanserleri ile ilişkili bulunmuştur. Enfeksiyonla indüklenen inflamasyon S100A8/A9 sekresyonunun temel kaynaklarındandır. Gut, diyabet ve obezite gibi metabolik inflamatuvar hastalıklarda S100A8/A9 serum ve inflamatuvar bölgelerde artmış miktarlarda saptanır. S100A11 yolağı genellikle osteoartrit patogenezi ile ilişkilidir. S100A12 artrit, vaskülit ve inflamatuvar barsak hastalıkları ile enfeksiyonlarla ilişkilidir.S100B’nin Alzheimer ve inflamatuvar barsak hastalıklarında da rolü vardır.

S100 proteins are small (10–12 kDa), calcium binding acidic cytosolic proteins which has a solubility in 100% ammonium sulfate . Upon calcium binding, S100 proteins undergo conformational changes enabling them to bind to specific ligands or receptors. Common to almost all S100 proteins is their ability to form homodimers and/or heterodimers. S100 proteins have functions of cell proliferation, protein phosphorylation , differentiation, energy metabolism, Ca2+ homeostasis, inflammation, and cell death. Expression of S100 proteins is altered in a variety of diseases, including cardiomyopathies, diseases of the central nervous system (CNS; such as Alzheimer disease), cancer and inflammatory disorders. S100A4 is a promising candidate biomarker in early cancer diagnosis and for the prediction of cancer metastasis. S100A7 is overexpressed in hyperproliferative andinflammatory skin diseases and an altered expression of this protein is associated with epithelial skin tumours. Infection-induced inflammation is one of the main resources for S100A8/A9 secretion. In metabolic inflammatory diseases, such as gout, diabetes, and obesity, S100A8/A9 is secreted and distributed in a disease-specific manner, and elevated levels of S100A8/A9 have been detected in sera and inflammatory sites. S100A11 pathway is particularly relevant for the pathogenesis of osteoarthritis. S100A12 proteins are associated with disease activity in many inflammatory diseases (including arthritis, vasculitis and inflammatory bowel disease) and infections. Pathogenic roles for extracellular S100B have been proposed in Alzheimer disease and in inflammatory bowel disease.

Keywords

İnflamasyon, S100 proteinleri, Inflammation, S100 Proteins

References

• 1. Austermann J, Zenker S, Roth J. S100-alarmins: potential therapeutic targets for arthritis. Expert opinion on therapeutic targets. 2017;21(7):739-51. 2. Chan JK, Roth J, Oppenheim JJ, Tracey KJ, Vogl T, Feldmann M, et al. Alarmins: awaiting a clinical response. The Journal of clinical investigation. 2012;122(8):2711-9. 3. Foell D, Kucharzik T, Kraft M, Vogl T, Sorg C, Domschke W, et al. Neutrophil derived human S100A12 (EN-RAGE) is strongly expressed during chronic active inflammatory bowel disease. Gut. 2003;52(6):847-53. 4. Foell D, Wittkowski H, Roth J. Mechanisms of disease: a 'DAMP' view of inflammatory arthritis. Nature clinical practice Rheumatology. 2007;3(7):382-90. 5. Donato R, Cannon BR, Sorci G, Riuzzi F, Hsu K, Weber DJ, et al. Functions of S100 proteins. Current molecular medicine. 2013;13(1):24-57. 6. Vogl T, Tenbrock K, Ludwig S, Leukert N, Ehrhardt C, van Zoelen MA, et al. Mrp8 and Mrp14 are endogenous activators of Toll-like receptor 4, promoting lethal, endotoxin-induced shock. Nature medicine. 2007;13(9):1042-9. 7. Sorci G, Riuzzi F, Giambanco I, Donato R. RAGE in tissue homeostasis, repair and regeneration. Biochimica et biophysica acta. 2013;1833(1):101-9. 8. Gebhardt C, Riehl A, Durchdewald M, Nemeth J, Furstenberger G, Muller-Decker K, et al. RAGE signaling sustains inflammation and promotes tumor development. The Journal of experimental medicine. 2008;205(2):275-85. 9. Kligman D, Hilt DC. The S100 protein family. Trends Biochem Sci. 1988;13(11):437-43. 10. Fei F, Qu J, Li C, Wang X, Li Y, Zhang S. Role of metastasis-induced protein S100A4 in human non-tumor pathophysiologies. Cell & bioscience. 2017;7(1):64. 11. Tomcik M, Palumbo-Zerr K, Zerr P, Avouac J, Dees C, Sumova B, et al. S100A4 amplifies TGF-beta-induced fibroblast activation in systemic sclerosis. Ann Rheum Dis. 2015;74(9):1748-55. 12. Austermann J, Spiekermann C, Roth J. S100 proteins in rheumatic diseases. Nature reviews Rheumatology. 2018;14(9):528-41. 13. Wolf R, Howard OM, Dong HF, Voscopoulos C, Boeshans K, Winston J, 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. Journal of immunology (Baltimore, Md : 1950). 2008;181(2):1499-506. 14. Holzinger D, Nippe N, Vogl T, Marketon K, Mysore V, Weinhage T, et al. Myeloid-related proteins 8 and 14 contribute to monosodium urate monohydrate crystal-induced inflammation in gout. Arthritis & rheumatology (Hoboken, NJ). 2014;66(5):1327-39. 15. Oliva K, Barker G, Rice GE, Bailey MJ, Lappas M. 2D-DIGE to identify proteins associated with gestational diabetes in omental adipose tissue. The Journal of endocrinology. 2013;218(2):165-78. 16. Murray PJ. Obesity corrupts myelopoiesis. Cell metabolism. 2014;19(5):735-6. 17. Wang S, Song R, Wang Z, Jing Z, Wang S, Ma J. S100A8/A9 in Inflammation. Frontiers in immunology. 2018;9. 18. Tyden H, Lood C, Gullstrand B, Jonsen A, Ivars F, Leanderson T, et al. Pro-inflammatory S100 proteins are associated with glomerulonephritis and anti-dsDNA antibodies in systemic lupus erythematosus. Lupus. 2017;26(2):139-49. 19. van den Bosch MH, Blom AB, Schelbergen RF, Koenders MI, van de Loo FA, van den Berg WB, et al. Alarmin S100A9 Induces Proinflammatory and Catabolic Effects Predominantly in the M1 Macrophages of Human Osteoarthritic Synovium. J Rheumatol. 2016;43(10):1874-84. 20. de Munter W, Geven EJ, Blom AB, Walgreen B, Helsen MM, Joosten LA, et al. Synovial macrophages promote TGF-beta signaling and protect against influx of S100A8/S100A9-producing cells after intra-articular injections of oxidized low-density lipoproteins. Osteoarthritis and cartilage. 2017;25(1):118-27. 21. He H, Li J, Weng S, Li M, Yu Y. S100A11: diverse function and pathology corresponding to different target proteins. Cell biochemistry and biophysics. 2009;55(3):117-26. 22. Andres Cerezo L, Sumova B, Prajzlerova K, Veigl D, Damgaard D, Nielsen CH, et al. Calgizzarin (S100A11): a novel inflammatory mediator associated with disease activity of rheumatoid arthritis. Arthritis Res Ther. 2017;19(1):79. 23. Foell D, Wittkowski H, Vogl T, Roth J. S100 proteins expressed in phagocytes: a novel group of damage-associated molecular pattern molecules. Journal of leukocyte biology. 2007;81(1):28-37. 24. Donato R, Sorci G, Riuzzi F, Arcuri C, Bianchi R, Brozzi F, et al. S100B's double life: intracellular regulator and extracellular signal. Biochimica et biophysica acta. 2009;1793(6):1008-22. 25. Yammani RR. S100 proteins in cartilage: role in arthritis. Biochimica et Biophysica Acta (BBA)-Molecular Basis of Disease. 2012;1822(4):600-6. 26. Capoccia E, Cirillo C, Gigli S, Pesce M, D'Alessandro A, Cuomo R, et al. Enteric glia: A new player in inflammatory bowel diseases. International journal of immunopathology and pharmacology. 2015;28(4):443-51.