Lehrstuhl für Haut- und Geschlechtskrankheiten
Josef-Schneider-Str. 2, 97080 Würzburg
Other participating persons and organisations:
Research foci (and basic equipment-based research projects):
Molecular mechanisms of endothelial activation.
Molecular mechanisms of keratinocyte proliferation and differentiation.
Molecular mechanisms of endothelial activation.
The activation of endothelial cells is a key process promoting initiation of inflammatory reactions. It is associated with a multistep cascade of events that results in the local recruitment of leukocytes to sites of inflammatory challenge. The process of endothelial activation underlies tight regulatory control mechanisms. Our interest is to study intracellular mechanisms of signal transduction which result in activation of endothelium. Central for our studies was the analysis of the IKK/IkappaB/NF-kappaB pathway and its crosstalk with mitogen-activated protein kinases, especially the MKK6/p38 signalling cascade.
Project 1 - relevant publications 1999-2001:
Goebeler M, Kilian K, Gillitzer R, Kunz M, Yoshimura T, Bröcker EB, Rapp UR, Ludwig S: The MKK6/p38 stress kinase cascade is involved in TNF-alpha-induced expression of monocyte chemoattractant protein-1 in endothelial cells. Blood 93, 857-865 (1999)
Hippenstiel S, Soeth S, Kellas B, Fuhrman O, Seybold J, Krüll M, von Eichel Streiber C, Goebeler M, Ludwig S, Suttorp N: Rho proteins and p38-MAPK pathway are important mediators for LPS-induced interleukin-8 expression in human endothelial cells. Blood 95, 3044-3051 (2000)
Goebeler M, Gillitzer R, Kilian K, Utzel K, Bröcker EB, Rapp UR, Ludwig S: Multiple signaling pathways regulate NF-kappaB-dependent transcription of the monocyte chemoattractant protein-1 (MCP-1) gene in primary endothelial cells. Blood 97, 46-55 (2001)
Goebeler M*, Trautmann A*, Toksoy A, Voß A, Bröcker EB, Gillitzer R: Sequential expression of multiple chemokines during elicitation of allergic contact dermatitis. Am J Pathol 158, 431-440 (2001) (* shared first authorship)
Gillitzer R, Goebeler M: Chemokines in cutaneous wound healing. J Leukoc Biol 69, 513-521 (2001)
Denk A*, Goebeler M*, Schmid S, Berberich I, Ritz O, Lindemann D, Ludwig S, Wirth T: Activation of NF-kappaB via the IkappaB kinase complex is both essential and sufficient for proinflammatory gene expression in primary endothelial cells. J Biol Chem 276, 28451-28458 (2001) (* shared first authorship)
Roth J, Goebeler M, Ludwig S, Wagner L, Kilian K, Sorg C, Harms E, Schulze-Osthoff K, Koch HG: Homocysteine inhibits tumor necrosis factor-induced activation of endothelium via modulation of nuclear factor-kappaB activity. Biochim Biophys Acta 1540, 154-165 (2001)
Molecular mechanisms of keratinocyte proliferation and differentiation
The epidermis is a regenerative organ subjected to permanent turnover throughout the life of an organism. In healthy skin, there is a balance between proliferation and of mitotically active keratinocytes in the innermost basal layer and differentiation of post-mitotic cells within the suprabasal layers of the epithelium. Signalling pathways known to be crucially involved in the regulation of growth and proliferation of keratinocytes are the Raf/MEK/ERK kinase cascade and the IKK/IkappaB/NFkappaB signalling pathway. We are studying the influence of both using models of calcium-induced differentiation of primary human keratinocytes and HaCaT cells.
In a second part of this project we are studying the role of calcium-binding proteins of the S100 family during differentiation of keratinocytes.
Project 2 - relevant publications 1999-2001:
Schmidt M, Goebeler M, Posern G, Feller SM, Seitz CS, Bröcker EB, Rapp UR, Ludwig S: Ras-independent activation of the Raf/MEK/Erk pathway upon calcium-induced differentiation of keratinocytes. J Biol Chem 275, 41011-41017 (2000)
Roth J, Goebeler M, Sorg C: S100A8 and S100A9 in inflammatory diseases. The Lancet 357, 1041 (2001)
Schmidt M, Gillitzer R, Toksoy A, Paus R, Bröcker EB, Rapp UR, Roth J, Ludwig S, Goebeler M: Selective expression of calcium-binding proteins S100A8 and S100A9 at distinct sites of hair follicles. J Invest Dermatol 117, 748-750 (2001)
Pasparakis M, Courtois G, Hafner M, Schmidt-Supprian M, Nenci A, Toksoy A, Krampert M, Goebeler M, Gillitzer R, Israel A, Krieg T, Rajewsky K, Haase I: TNF-mediated inflammatory skin disease in mice with epidermis-specific deletion of IKK2. Nature 417, 861-866 (2002)
Rewards and prizes:
Award of the "Jubiläumsstiftung zum 400-jährigen Bestehen der Bayerischen Julius-Maximilians-Universität Würzburg", July 1998;
Poster award of the "Arbeitsgemeinschaft Dermatologische Forschung (ADF)", Vienna, February 2000;
Poster award of the "Arbeitsgemeinschaft Dermatologische Forschung (ADF)", Munich, February 2001;