The Institut für Allgemeine Pharmakologie und Toxikologie at the Goethe University is experienced in the development and testing of new pharmacological substances. The head of the research team is Prof. Josef Pfeilschifter who is also the head of the Institute with a staff of seven senior scientists and over 30 academic co-workers. This group´s main interest is on the molecular mechanisms of inflammation that underlie the “cardinal symptoms of inflammation” including redness, heat, swelling and pain. These symptoms are due to vasodilatation in pericapillary beds and increased vascular permeability to solutes, followed rapidly by neutrophil and other inflammatory cell infiltration. The complexity of this stage is reflected in the large number of inflammatory mediators that are synthesised and released in response to an injurious agent. In addition the Institute´s interest is the characterisation of signalling pathways and functions of various inflammatory cytokines, particularly those related to lipid signalling. The functional relevance of these mediators is evaluated in various experimental models of glomerulonephritis, hemorrhagic shock, endotoxemia and cutaneous wound healing. The latter prototypically reflects processes that generally occur also in kidney injury and regeneration.

Prof. Andrea Huwiler and Dr. Karl-Friedrich Beck will be in charge of the work related to the EICOSANOX integrated project.

References:
Goren, I., Kämpfer, H., Podda, M. , Pfeilschifter J. & Frank, S. (2003) Leptin and wound inflammation in diabetic ob/ob mice: differential regulation of neutrophil and macrophage influx and a potential role for the scab as a sink for inflammatory cells and mediators. Diabetes 52, 2821-2832

Huwiler, A., Akool, el-S., Ashrafi, A., Hamada, F.M., Pfeilschifter, J. & Eberhardt, W. (2003) ATP potentiates interleukin-1 b-induced MMP-9 expression in mesangial cells via recruitment of the ELAV protein HuR. J. Biol. Chem. 278, 51758-51769

Akool, el-S., Kleinert, H., Hamada, F.M., Abdelwahab, M.H. Forstermann, U., Pfeilschifter, J. & Eberhardt, W. (2003) Nitric oxide increases the decay of matrix metalloproteinase 9 mRNA by inhibiting the expression of mRNA-stabilizing factor HuR. Mol. Cell. Biol. 23, 4901-4916

Huwiler, A. & Pfeilschifter, J. (2003) Nitric oxide signalling with a special focus on lipid-derived mediators Biol. Chem. 384, 1379-1389

Beck, S., Lambeau, G., Scholz-Pedretti, K., Gelb, M.H., Janssen, M.J., Edwards, S.H., Wilton, D.C., Pfeilschifter, J. & Kaszkin, M. (2003) Potentiation of tumor necrosis factor a-induced secreted phospholipase A2 (sPLA2)-IIA expression in mesangial cells by an autocrine loop involving sPLA2 and peroxisome proliferator-activated receptor a activation. J. Biol. Chem. 278, 29799-29812

Schaefer, L., Beck, K.F., Raslik, I., Walpen, S., Mihalik, D., Micegova, M., Macakova, K., Schonherr, E., Seidler, D.G., Varga, G., Schaefer R.M., Kresse, H. & Pfeilschifter, J. (2003) Biglycan, a nitric oxide-regulated gene, affects adhesion, growth, and survival of mesangial cells.. J. Biol. Chem. 278, 26227-26237.

Franzen, R., Fabbro, D., Aschrafi, A., Pfeilschifter, J., & Huwiler, A. (2002) Nitric oxide induces degradation of the neutral ceramidase in rat renal mesangial cells and is counterregulated by protein kinase C. J. Biol. Chem 277, 46184-46190