Immune
Pharmacology and Clinical Immunology
- Chronic Inflammation: chemokines, dendritic cell
differentiation and sphingolipids -
Prof. Dr. med. Heinfried H. Radeke
Phone: + 49 69 6301-83104 or -83109
Fax: +49 69 6301-83202
e-mail: radeke@em.uni-frankfurt.de
personal webpage: www.radeke.de
Vorlesungen+Kurse / Lectures of Prof. Radeke (also at the eLearning platform of Goethe University Frankfurt: WebCT)
Member of ZAFES (Zentrum
für Arzneimittel-Forschung, -Entwicklung und Sicherheit)
Deputy Speaker of DFG-Graduate Study Program 1172 („Biologicals" - Research, Development and Safety of Biopharmaceutical Drugs)
integrated part of FIRST
Member of LIFF
Co-worker:
Dr. phil.nat. Carolin Daniel
Dr. rer.med. Cornelia Richter (M.Sc. Biotechnology)
cand. phil.nat. Oliver Giegold (M.Sc. Pharmacy)
cand. phil.nat. Matthias Schröder (Dipl. Biol.)
cand. phil.nat. Christina Neske (Dipl. Biol.)
Martina Herrero San Juan
cand.Dipl.Biol. Fatima Simsek
cand. med. Katja Rüger
cand. med. dent. Nash'ta Rave
cand.med. Elisabeth Katzy
cand.med. Claudia Hofschulte
cand. med. Nico Söhling
Principle Research Interest:
|
Infiltrates of mononuclear cells represent
the hallmark of Chronic Inflammation. Following tissue injury
cells of the innate (PDF1)
and adaptive immune system (PDF2+3)
invade the respective area through their interaction with adhesion
molecules and chemotactic factors, such as bacterial components,
lipids, complement (PDF4+5)
fragments and chemokines.
Especially chemokines are released from local cells with a tissue
specific pattern. First line chemokines include phagocyte attracting
interleukin-8 and monocyte-chemoattractive- peptide-1 (MCP-1). Additionally,
during late acute and in the chronic phase of inflammation immigrated
macrophages and lymphocytes contribute to the chemokine gradient
by releasing specific chemokines such as RANTES: 'regulated upon activation, normal T cell expressed
and secreted', and the CXCR3 ligands, MIG, IP-10 and I-TAC. Moreover, chronic inflammation is specifically characterized by pathological homing, and pathological activities of otherwise homeostatic chemokines (e.g. CXCL12) leading to tertiary lymphoid structures. |
|
|
|
The interaction of the injurious agent and
local cells with the professional immune system will have
an decisive influence on the transition from acute to chronic
inflammation, a process finally destroying vital organ function |
- top of page -
|
With chronic, immune-mediated nephritis as an example our research interest focuses on the interaction of renal glomerular mesangial cells with lymphocytes and antigen-presenting cells, such as dendritic cells. Dependent on the genetic background and the injurious agent different forms of nephritis may be initiated and propagated by primarily T helper-1 or T helper-2 type of effector mechanisms.On the basis of a further characterization of this local cell - immune cell interaction the pharmacological target of our research interests is the blockade of synthesis, migratory action and receptor signalling of chemokines. |
- top of page -
Current Projects:
|
|
The role of renal glomerular
mesangial cells for the activation and differentiation of
dendric cells and T lymphocytes Factors released by local tissue cells, such as chemokines and prostaglandins may have an decisive influence on the invading immune cells. Using FACS, ELISPOT, and cDNA-array technology we will determine the effects of these local factors on the activation and frequency of cytokine secreting antigen presenting cells and lymphocytes. |
|
|
Large scale eukaryotic expression in yeast
and biological in vitro and in vivo characterization of chemokine
antagonists Chemokine antagonists such as N-terminal truncated MCP-1 and HHV8 derived viral MIP-II have been cloned and proteins are produced in a pichia pastoris expression system. Using high density computer-assisted culture systems and large scale purification protocols (in cooperation with R. Luttmann, G. Cornelissen, E. Werner, Hamburg) the yield increases to mg amounts. Subsequently antagonistic properties will be characterized with 96-well chemotaxis, migration assays and receptor binding and signaling studies. |
|
|
Modulation of immune cell function by bioactive
lipids. Bioactive lipids such as sphingosine 1-phosphate (S1P), its analog FTY720 (PDF), prostaglandins (PGE2, PGD2) or vitamin D3 (PDF) modulate fundamental immunological processes in the context of cell proliferation, migration and inflammatory gene expression. Using dendritic cell maturation and T lymphocyte polarization as in vitro models (PDF) and colitis as in vivo model (PDF) our experimental work is focused on the functional characterization of these immune modulators. Furthermore, as immune cells express multiple subsets of lipid receptors and sphingolipid enzymes, antisense oligonucleotides, lentiviral shRNA vectors, as well as diverse knockout mouse models are applied to analyze specific receptors and sphingolipid enzymes. |