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Institut für Experimentelle Dermatologie	Tel. (0251) 83-56577 Fax: (0251) 83-56578 e-mail: sorg@uni-muenster.de www:  http://medweb.uni-muenster.de/institute/ederma
Röntgenstr. 21 48149 Münster Direktor: Univ.-Prof. Dr. Clemens Sorg
Forschungsschwerpunkte 2003 - 2004    zurück    weiter

Molekularbiologische und biochemische Zusammenhänge von akuten und chronischen Entzündungen   Die Forschungsarbeiten im Institut beschäftigen sich mit molekularbiologischen und biochemischen Zusammenhängen von akuten und chronischen Entzündungen. Genexpressionsanalysen von aktivierten Zielzellen im Vergleich zu Kontrollzellen liefern die Basis für weitergehende Analysen. Im Fokus stehen die drei S100 Proteine S100A8, S100A9 und S100A12, die spezifisch nur in myeloiden Zellen exprimiert werden und deren Funktionen gegenwärtig untersucht werden. Ein weiteres Forschungsgebiet ist die Charakterisierung des Scavengerrezeptors CD163 in Monozyten. Im Besonderen werden Einflüsse von Proteinmodifikationen und möglicher Interaktionspartner im Hinblick auf ihre biologische Bedeutungen untersucht. In diesem Kontext wird auch der Bedeutung des Ca2+, das als 'second messenger' Signale auf das submembranöse Zytoskelett überträgt, besondere Aufmerksamkeit geschenkt. Beteiligte Wissenschaftler: Prof. Dr. Clemens Sorg, Prof. Dr. Johannes Roth, Dr. Martina Ahlmann, Dr. Katarzyna Barczyk, Konrad Benedyk, Malgorzata Benedyk, Dr. Günter Bode, Dr. Jan Ehrchen, Dr. Dirk Föll, PD Dr. Claus Kerkhoff, Dr. Nadja Leukert, Dr. Harutyun Melkonyan, Dr. Wolfgang Nacken, Kirsten Roebrock, Dr. Claudia Sopalla, Dr. Lars Steinmüller, Dr. Klaus Tenbrock, Dr. Dorothee Viemann, Dr. Thomas Vogl, Dr. Helmut Wittkowski Veröffentlichungen: Wulffraat NM, Haas PJ, Frosch M, de Kleer IM, Vogl T, Brinkman DMC, Quartier P, Roth J, Kuis W. Myeloid related protein 8 and 14 secretion reflects phagocyte activation and correlates with disease activity in juvenile idiopathic arthritis treated with autologous stem cell transplantation. Annals of the Rheumatic Diseases.62:236-241 (2003) von Stebut E, Ehrchen JM, Belkaid Y, Kostka SL, Molle K, Knop J, Sunderkotter C, Udey MC. Interleukin 1 alpha promotes Th-1 differentiation and inhibits disease progression in Leishmania major - Susceptible BALB/c mice. Journal of Experimental Medicine.198:191-199 (2003) van Lent P, Nabbe KC, Boross P, Blom AB, Roth J, Holthuysen A, Sloetjes A, Verbeek S, van den Berg W. The inhibitory receptor Fc gamma RII reduces joint inflammation and destruction in experimental immune complex-mediated arthritides not only by inhibition of Fc gamma RI/III but also by efficient clearance and endocytosis of immune complexes. American Journal of Pathology.163:1839-1848 (2003) Stroh C, Held E, Samraj AK, Schulze-Osthoff K. Specific inhibition of transcription factor NF-kappa B through intracellular protein delivery of I kappa B alpha by the Herpes virus protein VP22. Oncogene.22:5367-5373 (2003) Seeliger S, Vogl T, Engels IH, Schroder JM, Sorg C, Sunderkotter C, Roth J. Expression of Calcium-Binding Proteins MRP8 and MRP14 in Inflammatory Muscle Diseases. Am J Pathol.163:947-956. (2003) Seeliger S, Derian CK, Vergnolle N, Bunnett NW, Nawroth R, Schmelz M, von der Weid PY, Buddenkotte J, Sunderkotter C, Metze D, Andrade-Gordon P, Harms E, Vestweber D, Luger TA, Steinhoff M. Proinflammatory role of proteinase-activated receptor-2 in humans and mice during cutaneous inflammation in vivo. Faseb Journal.17:1871-1885 (2003) Schonlau F, Schlesiger C, Ehrchen J, Grabbe S, Sorg C, Sunderkotter C. Monocyte and macrophage functions in M-CSF-deficient op/op mice during experimental leishmaniasis. Journal of Leukocyte Biology.73:564-573 (2003) Scholzen TE, Sunderkotter C, Kalden DH, Brzoska T, Fastrich M, Fisbeck T, Armstrong CA, Ansel JC, Luger TA. alpha-melanocyte stimulating hormone prevents lipopolysaccharide-induced vasculitis by down-regulating endothelial cell adhesion molecule expression. Endocrinology.144:360-370 (2003) Rudack C, Maune S, Eble J, Schroeder JM. The primary role in biologic activity of the neutrophil chemokines IL-81 and GRO-alpha in cultured nasal epithelial cells. Journal of Interferon and Cytokine Research.23:113-123 (2003) Roth J, Vogl T, Sorg C, Sunderkotter C. Phagocyte-specific S100 proteins: a novel group of proinflammatory molecules. Trends in Immunology.24:155-158 (2003) Roth J, Vogl T, Sunderkotter C, Sorg C. Chemotactic activity of S100A8 and S100A9. Journal of Immunology.171:5651-5651 (2003) Renz A, Los M. Comments on the estimation of cell membrane alteration after drug treatment by LDH release - Response. Blood.101:2895-2895 (2003) Nacken W, Roth J, Sorg C, Kerkhoff C. S100A9/S100A8: Myeloid representatives of the S100 protein family as prominent players in innate immunity. Microscopy Research and Technique.60:569-580 (2003) Manitz MP, Horst B, Seeliger S, Strey A, Skryabin BV, Gunzer M, Frings W, Schonlau F, Roth J, Sorg C, Nacken W. Loss of S100A9 (MRP14) results in reduced interleukin-8-induced CD11b surface expression, a polarized microfilament system, and diminished responsiveness to chemoattractants in vitro. Molecular and Cellular Biology.23:1034-1043 (2003) Maeda SM, Rotta O, Michalany NS, Camargo ZP, Sunderkotter C, Tomimori-Yamashita J. Comparison between anti-PGL-I serology and Mitsuda reaction: clinical reading, microscopic findings and immunohistochemical analysis. Leprosy Review.74:263-274 (2003) Los M, Burek CJ, Stroh C, Benedyk K, Hug H, Mackiewicz A. Anticancer drugs of tomorrow: apoptotic pathways as targets for drug design. Drug Discovery Today.8:67-77 (2003) Kess D, Peters T, Zamek J, Wickenhauser C, Tawadros S, Loser K, Varga G, Grabbe S, Nischt R, Sunderkotter C, Muller W, Krieg T, Scharffetter-Kochanek K. CD4(+) T cell-associated pathophysiology critically depends on CD18 gene dose effects in a murine model of psoriasis. Journal of Immunology.171:5697-5706 (2003) Fuellen G, Foell D, Nacken W, Sorg C, Kerkhoff C. Absence of S100A12 in mouse: implications for RAGE-S100A12 interaction. Trends in Immunology.24:622-624 (2003) Frosch M, Vogl T, Seeliger S, Wulffraat N, Kuis W, Viemann D, Foell D, Sorg C, Sunderkotter C, Roth J. Expression of myeloid-related proteins 8 and 14 in systemic-onset juvenile rheumatoid arthritis. Arthritis and Rheumatism.48:2622-2626 (2003) Foell D, Ichida F, Vogl T, Yu XY, Chen R, Miyawaki T, Sorg C, Roth J. S100A12 (EN-RAGE) in monitoring Kawasaki disease. Lancet.361:1270-1272 (2003) Foell D, Kucharzik T, Kraft M, Vogl T, Sorg C, Domschke W, Roth J. Neutrophil derived human S100A12 (EN-RAGE) is strongly expressed during chronic active inflammatory bowel disease. Gut.52:847-853 (2003) Foell D, Seeliger S, Vogl T, Koch HG, Maschek H, Harms E, Sorg C, Roth J. Expression of S100A12 (EN-RAGE) in cystic fibrosis. Thorax.58:613-617 (2003) Foell D, Kane D, Bresnihan B, Vogl T, Nacken W, Sorg C, FitzGerald O, Roth J. Expression of the pro-inflammatory protein S100A12 (EN-RAGE) in rheumatoid and psoriatic arthritis. Rheumatology.42:1383-1389 (2003) Cassens U, Lewinski G, Samraj AK, von Bernuth H, Baust H, Khazaie K, Los M. Viral modulation of cell death by inhibition of caspases. Archivum Immunologiae Et Therapiae Experimentalis.51:19-27 (2003) Baust H, Schoke A, Brey A, Gern U, Los M, Schmid RM, Rottinger EM, Seufferlein T. Evidence for radiosensitizing by gliotoxin in HL-60 cells: implications for a role of NF-kappa B independent mechanisms. Oncogene.22:8786-8796 (2003) Blom, A.B., P. van Lent, A.E.M. Holthuysen, P.M. van der Kraan, J. Roth, N. van Rooijen, and W.B. van den Berg. 2004. Synovial lining macrophages mediate osteophyte formation during experimental osteoarthritis. Osteoarthritis and Cartilage 12:627-635. Bohm, M., M. Raghunath, C. Sunderkotter, M. Schiller, S. Stander, T. Brzoska, T. Cauvet, H.B. Schioth, T. Schwarz, and T.A. Luger. 2004. Collagen metabolism is a novel target of the neuropeptide alpha-melanocyte-stimulating hormone. Journal of Biological Chemistry 279:6959-6966. Drevets, D.A., M.J. Dillon, J.S. Schawang, N. van Rooijen, J. Ehrchen, C. Sunderkotter, and P.J.M. Leenen. 2004. The Ly-6C(high) monocyte subpopulation transports Listeria monocytogenes into the brain during systemic infection of mice. Journal of Immunology 172:4418-4424. Ehrchen, J., A. Sindrilaru, S. Grabbe, F. Schonlau, C. Schlesiger, C. Sorg, K. Scharffetter-Kochanek, and C. Sunderkotter. 2004. Senescent BALB/c mice are able to develop resistance to Leishmania major infection. Infection and Immunity 72:5106-5114. Foell, D., J. Hernandez-Rodriguez, M. Sanchez, T. Vogl, M.C. Cid, and J. Roth. 2004. Early recruitment of phagocytes contributes to the vascular inflammation of giant cell arteritis. Journal of Pathology 204:311-316. Foell, D., M. Frosch, C. Sorg, and J. Roth. 2004. Phagocyte-specific calcium-binding S100 proteins as clinical laboratory markers of inflammation. Clinica Chimica Acta 344:37-51. Foell, D., H. Wittkowski, I. Hammerschmidt, N. Wulffraat, H. Schmeling, M. Frosch, G. Horneff, W. Kuis, C. Sorg, and J. Roth. 2004. Monitoring neutrophil activation in juvenile rheumatoid arthritis by S100A12 serum concentrations. Arthritis and Rheumatism 50:1286-1295. Foell, D., M. Frosch, A.S. zur Wiesch, T. Vogl, C. Sorg, and J. Roth. 2004. Methotrexate treatment in juvenile idiopathic arthritis: when is the right time to stop? Annals of the Rheumatic Diseases 63:206-208. Foell, D., and J. Roth. 2004. Proinflammatory S100 proteins in arthritis and autoimmune disease. Arthritis Rheum 50:3762-3771. Frosch, M., and D. Foell. 2004. Wegener granulomatosis in childhood and adolescence. European Journal of Pediatrics 163:425-434. Frosch, M., T. Vogl, R. Waldherr, C. Sorg, C. Sunderkotter, and J. Roth. 2004. Expression of MRP8 and MRP14 by macrophages is a marker for severe forms of glomerulonephritis. Journal of Leukocyte Biology 75:198-206. Fuellen, G., D. Foell, W. Nacken, C. Sorg, and C. Kerkhoff. 2003. Absence of S100A12 in mouse: implications for RAGE-S100A12 interaction. Trends in Immunology 24:622-624. Ghavami, S., C. Kerkhoff, M. Los, M. Hashemi, C. Sorg, and F. Karami-Tehrani. 2004. Mechanism of apoptosis induced by S100A8/A9 in colon cancer cell lines: the role of ROS and the effect of metal ions. Journal of Leukocyte Biology 76:169-175. Kreuter, M., C. Langer, C. Kerkhoff, P. Reddanna, A.L. Kania, S. Maddika, K. Chlichlia, T.N. Bui, and M. Los. 2004. Stroke, myocardial infarction, acute and chronic inflammatory diseases: caspases and other apoptotic molecules as targets for drug development. Archivum Immunologiae Et Therapiae Experimentalis 52:141-155. Nacken, W., C. Sorg, and C. Kerkhoff. 2004. The myeloid expressed EF-hand proteins display a diverse pattern of lipid raft association. Febs Letters 572:289-293. Philchenkov, A., M. Zavelevich, T.J. Kroczak, and M. Los. 2004. Caspases and cancer: Mechanisms of inactivation and new treatment modalities. Experimental Oncology 26:82-97. Schachtrup, C., T.E. Scholzen, V. Grau, T.A. Luger, C. Sorg, F. Spener, and C. Kerkhoff. 2004. L-FABP is exclusively expressed in alveolar macrophages within the myeloid lineage - Evidence for a PPAR alpha-independent expression. International Journal of Biochemistry & Cell Biology 36:2042-2053. Schoenlau, F., C. Schlesiger, J. Ehrehen, S. Grabbe, C. Sorg, and C. Sunderkotter. 2003. Monocyte and macrophage functions in M-CSF-deficient op/op mice during experimental leishmaniasis. Journal of Leukocyte Biology 73:564-573. Schulze zur Wiesch, A., D. Foell, M. Frosch, T. Vogl, C. Sorg, and J. Roth. 2004. Myeloid related proteins MRP8/MRP14 may predict disease flares in juvenile idiopathic arthritis. Clin Exp Rheumatol 22:368-373. Sunderkotter, C., J. Roth, and G. Bonsmann. 2004. Leukocytoclastic vasculitis. Hautarzt 55:759-783. Sunderkotter, C., T. Nikolic, M.J. Dillon, N. van Rooijen, M. Stehling, D.A. Drevets, and P.J.M. Leenen. 2004. Subpopulations of mouse blood monocytes differ in maturation stage and inflammatory response. Journal of Immunology 172:4410-4417. Sunderkotter, C.H., J. Tomimori-Yamashita, V. Nix, S.M. Maeda, A. Sindrilaru, M. Mariano, C. Sorg, and J. Roth. 2004. High expression of myeloid-related proteins 8 and 14 characterizes an inflammatorily active but ineffective response of macrophages during leprosy. Immunology 111:472-480. Timmermann, M., F. Buck, C. Sorg, and P. Hogger. 2004. Interaction of soluble CD163 with activated T lymphocytes involves its association with non-muscle myosin heavy chain type A. Immunology and Cell Biology 82:479-487. Viemann, D., M. Goebeler, S. Schmid, K. Klimmek, C. Sorg, S. Ludwig, and J. Roth. 2004. Transcriptional profiling of IKK2/NF-kappa B- and p38 MAP kinase-dependent gene expression in TNF-alpha-stimulated primary human endothelial cells. Blood 103:3365-3373. Vogl, T., S. Ludwig, M. Goebeler, A. Strey, I.S. Thorey, R. Reichelt, D. Foell, V. Gerke, M.P. Manitz, W. Nacken, S. Werner, C. Sorg, and J. Roth. 2004. MRP8 and MRP14 control microtubule reorganization during transendothelial migration of phagocytes. Blood 104:4260-4268. Vormoor, J., K. Ehlert, A.H. Groll, H.G. Koch, M. Frosch, and J. Roth. 2004. Successful hematopoietic stem cell transplantation in Farber disease. J Pediatr 144:132-134. Ye, F., D. Foell, K.I. Hirono, T. Vogl, C. Rui, X. Yu, S. Watanabe, K. Watanabe, K. Uese, I. Hashimoto, J. Roth, F. Ichida, and T. Miyawaki. 2004. Neutrophil-derived S100A12 is profoundly upregulated in the early stage of acute Kawasaki disease. Am J Cardiol 94:840-844.