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Buttgereit lab

How do immune cells adapt to oxygen and nutrient deficiencies in inflamed tissue?

Introduction
Members
Selected Publications
Cooperation partners

Acute and chronic inflammation can lead to a pronounced lack of oxygen and nutrients in the area of inflammation. How does the immune system manage to remain active despite this?

In acute inflammatory processes such as in the initial phase of a fracture hematoma and during tissue regeneration, but also in chronic inflammation, such as rheumatoid arthritis, cells sometimes need more nutrients and oxygen than the body provides. This can lead to hypoxia at the site of inflammation – a pronounced lack of these vital substances. In order to be able to continue functioning, immune cells and other cell types such as endothelial cells that accumulate in the area of inflammation or in a hematoma have a number of adaptation mechanisms, which finally re-establish homeostasis. Hypoxia driven angiogenesis is a fundamental process of tissue regeneration, inflammation but also tumor growth. It is regulated by the master regulators of adaptation to hypoxia, namely hypoxia-inducible factor (HIF)-1 and -2. Demonstrating the distinct functions HIF-1 and HIF-2 in bioenergetic adaption and angiogenic tubular formation, we also observed overlapping and in part redundant regulation of pro-angiogenic factors including the macrophage migration inhibitory factor. These kind of sophisticated cellular adaptation mechanisms are essential to re-balance a de-balanced system and therefore to determine fate and function of all cellular systems. These adaptation mechanisms also offer starting points for drug therapies, for example from the active substance classes of glucocorticoids and Disease-modifying anti-rheumatic drugs (DMARDs).

The adaptation mechanisms of immune cells to a changed microenvironment in inflammatory reactions differ from species to species. Therefore, we are establishing in vitro models based on human cells in order to mimic acute and chronic inflammation such as found in the initial phase of fracture healing and in the inflamed joint. To this end, we are generating a variety of different in vitro 3D disease models that exclusively consist of the involved human cells in shape with a 3D architecture under the influence of an inflammatory microenvironment. These models will provide tools for the analysis of arthritis and fracture healing as well as for preclinical drug screening and testing thereby reducing the amount of animal experiments.

Group Leader
    Prof. Dr. med. Frank Buttgereit

Prof. Dr. med. Frank Buttgereit

Department of Rheumatolgoy and Clinical Immunology, Charité – Universitätsmedizin Berlin
Charitéplatz 1
10117 Berlin
Charité Homepage
Gemany

Phone +49 (0)30 450 513 125
Fax +49 (0)30 450 513 917
frank.buttgereit@charite.de

Keywords
Bioenergetics of immune functions
Hypoxia and angiogenesis
Glucocorticoids
Autoimmune diseases
Fracture healing

Continue to Members

Groupleader:
Prof. Dr. med. Frank Buttgereit

Scientists:
Dr. rer. nat. Timo Gaber (Scientific head)
Dr. rer. nat. Cindy Strehl (Administrative head)
Dr. rer. nat. Dimas Abdirama
Dr. med. Sandra Hermann
Dr. vet. med. Annemarie Lang
Dr. med. Robert Biesen

Ph.D. Students:
Moritz Pfeiffenberger, M.Sc.
Alexandra Damerau, M.Sc.
Siska Wilantri, M.Sc.

MD Students:
Lisa Ehlers
Pierre-Louis Krauß
Franziska Heinsohn
Edgar Wiebe
Antonia Brinkman
Marie-Christin Weber
Kim Zeiner

Bachelor/Diploma/Master Students:
Justyna Pienczykowski

Technicians:
Manuela Jakstadt
Gabriele May

Students:
Pelle Löwe
Aditi Kuppe

Group Leader
    Prof. Dr. med. Frank Buttgereit

Prof. Dr. med. Frank Buttgereit

Department of Rheumatolgoy and Clinical Immunology, Charité – Universitätsmedizin Berlin
Charitéplatz 1
10117 Berlin
Charité Homepage
Gemany

Phone +49 (0)30 450 513 125
Fax +49 (0)30 450 513 917
frank.buttgereit@charite.de

Keywords
Bioenergetics of immune functions
Hypoxia and angiogenesis
Glucocorticoids
Autoimmune diseases
Fracture healing

Continue to Selected Publications

Gaber T, Strehl C, Buttgereit F. Metabolic regulation of inflammation. Nat Rev Rheumatol. 2017 May;13(5):267-279. doi: 10.1038/nrrheum.2017.37. Epub 2017 Mar 23. Review. PubMed PMID: 28331208.

Hahne M, Schumann P, Mursell M, Strehl C, Hoff P, Buttgereit F, Gaber T. Unraveling the role of hypoxia-inducible factor (HIF)-1α and HIF-2α in the adaption process of human microvascular endothelial cells (HMEC-1) to hypoxia: Redundant HIF-dependent regulation of macrophage migration inhibitory factor. Microvasc Res. 2018 Mar; 116:34-44. doi: 10.1016/j.mvr.2017.09.004. Epub 2017 Oct 6. PubMed PMID: 28993199.

Hoff P, Gaber T, Strehl C, Jakstadt M, Hoff H, Schmidt-Bleek K, Lang A, Röhner E, Huscher D, Matziolis G, Burmester GR, Schmidmaier G, Perka C, Duda GN, Buttgereit F. A Pronounced Inflammatory Activity Characterizes the Early Fracture Healing Phase in Immunologically Restricted Patients. Int J Mol Sci. 2017 Mar 8;18(3). pii: E583. doi: 10.3390/ijms18030583. PubMed PMID: 28282868; PubMed Central PMCID: PMC5372599.

Lang A, Volkamer A, Behm L, Röblitz S, Ehrig R, Schneider M, Geris L, Wichard J, Buttgereit F. In silico methods – Computational alternatives to animal testing. ALTEX. 2018;35(1):124-126. doi: 10.14573/altex.1712031. PubMed PMID: 29374440.

Cutolo M, Hopp M, Liebscher S, Dasgupta B, Buttgereit F. Modified-release prednisone for polymyalgia rheumatica: a multicentre, randomised, active-controlled, double-blind, parallel-group study. RMD Open. 2017 Mar 17;3(1): e000426. doi: 10.1136/rmdopen-2016-000426. eCollection 2017. PubMed PMID: 28405475; PubMed Central PMCID: PMC5372105.

Group Leader
    Prof. Dr. med. Frank Buttgereit

Prof. Dr. med. Frank Buttgereit

Department of Rheumatolgoy and Clinical Immunology, Charité – Universitätsmedizin Berlin
Charitéplatz 1
10117 Berlin
Charité Homepage
Gemany

Phone +49 (0)30 450 513 125
Fax +49 (0)30 450 513 917
frank.buttgereit@charite.de

Keywords
Bioenergetics of immune functions
Hypoxia and angiogenesis
Glucocorticoids
Autoimmune diseases
Fracture healing

Continue to Cooperation partners

Gerd-Rüdiger Burmester, Thomas Häupl, Alexander Scheffold, Jacqueline Detert, Eugen Feist, Charité – Universitätsmedizin Berlin, Department of Rheumatology and Clinical Immunology, Berlin, Germany

Georg N. Duda, Katharina Schmidt-Bleek, Charité – Universitätsmedizin Berlin, Berlin Brandenburg Center for Regenerative Therapies/ Julius-Wolff Institut, Berlin, Germany

Carsten Perka, Charité – Universitätsmedizin Berlin, Center for Musculoskeletal Surgery, Berlin, Germany

Yvonne Dörffel, Charité – Universitätsmedizin Berlin, Department of Gastroenterology and Hepatology, Berlin, Germany

Nicole Pischon, Katharina Gurzawska, Charité – Universitätsmedizin Berlin, Centrum für Zahn-, Mund- und Kieferheilkunde, Abteilung für Parodontologie und Synoptische Zahnmedizin, Berlin, Germany

Andreas Radbruch, Max Löhning, Deutsches Rheuma-Forschungszentrum, Cell Biology, Berlin, Germany

Roland Lauster, TU-Berlin, Medical Biotechnology, Berlin, Germany

Markus Seibel, Hong Zhou, University of Sydney, ANZAC Institute, Sydney, Australia

Dr. Stefan Krauss, Beth Israel Deaconess Medical Center, Harvard Medical School, and Merck Research Laboratories, Boston, USA

Jon Yewdell, National Institute of Allergy and Infectious Diseases, Cellular Biology Section, Bethesda, USA

Dr. Christian Abraham, Andreas Brandt, medac GmbH, Wedel, Deutschland

Douglas J. Veale, University College Dublin, The Conway Institute for Biomedical and Biomolecular Research, Dublin, Ireland

Prof. Susanna Röblitz und Dr. Rainald Ehrig, Konrad-Zuse-Zentrum Berlin

Dr. Dirk Barnwitz und Dr. Igor Ponomarev, fzmb GmbH Bad Langensalza

Dr. Paulin Jirkof, Institut für Experimentelle Chirurgie, UniversitätsSpital Zürich, Universität Zürich

Group Leader
    Prof. Dr. med. Frank Buttgereit

Prof. Dr. med. Frank Buttgereit

Department of Rheumatolgoy and Clinical Immunology, Charité – Universitätsmedizin Berlin
Charitéplatz 1
10117 Berlin
Charité Homepage
Gemany

Phone +49 (0)30 450 513 125
Fax +49 (0)30 450 513 917
frank.buttgereit@charite.de

Keywords
Bioenergetics of immune functions
Hypoxia and angiogenesis
Glucocorticoids
Autoimmune diseases
Fracture healing

Continue to Introduction