Adrenal Gland Microenvironment Regulation in Sepsis
Dr. rer. medic. Waldemar Kanczkowski, PhD
Principal Investigator
- 2000-2005 Master Studies, Intercollegiate Faculty of Biotechnology.
University of Gdansk & Medical University of Gdansk, Poland - 2005-2009 PhD Studies, Max Planck Institute for Cellular Biology and Genetics, Dresden (MPI-CBG), Germany
- 2009-2014 Postdoc, Medical Clinic III, TUD Dresden, Germany
- 2014-now Principal Investigator, Medical Clinic III, TUD Dresden, Germany
0351 458-6259/6130 E-Mail
The adrenal gland is a key effector component of a stress system in human body. Multiple, direct and paracrine interactions between different cell types and their progenitors take place within the adrenal gland microenvironment. The main interests of our group is to investigate how these unique interactions influence progression of several pathological conditions such as e.g. obesity or sepsis, and are in turn influenced by these disorders.
Adapted according to Kanczkowski et al., 2017 (7).
Past and Current work
Our previous studies funded by DFG as a part of Clinical Research Unit 252 (2011-17; KA 3013/2-2) demonstrated that both endotoxemia-provoked SIRS and cecal ligation and puncture (CLP)-induced sepsis in mice lead to systemic and adrenal gland inflammation. This process was associated with rapid immune cell infiltration and onset of cellular death of adrenal cells (2). Together with our collaborator Prof. Chavakis (IKL-KPB), we have identified that adrenal gland expresses developmental-endothelial locus-1 (Del-1) molecule, which is a gate keeper that controls adrenal gland inflammation during systemic inflammation induced by bacterial LPS (3). By engaging mice with tissue-specific inactivation of TLR signaling, we identified myeloid cells in the adrenal gland microenvironment as being crucial for hypothalamic-pituitary-adrenal (HPA) axis activation but also for adrenal inflammation (4).Furthermore, we have found that degree of adrenal gland inflammation and damage correlated with mortality rate of septic mice (6). Currently as a part of newly funded CRC/TRR 205 project (A01), we investigate the role of anaphylatoxins C3a, C5a and their receptors in the adrenal gland function and dysfunction during sepsis.
Adapted according to Kanczkowski et al., 2015 (5).
Group members
GROUP MEMBERS | Phone | |
|---|---|---|
Mariko Sue, MD PhD (Postdoc) | 0351 458-6606 | |
Alexia Belavgeni (PhD Candidate) | 0351 458-6606 | |
Maria Schuster (Animal care specialist & MTA): | 0351 458-6262 | |
Uta Lehnert ( Senior MTA) | 0351 458-6605 | |
Linda Friedrich (MTA) | 0351 458-6605 |
Selected publications on this topic
- Kanczkowski W, Tymoszuk P, Ehrhart-Bornstein M, Wirth MP, Zacharowski K, Bornstein SR. Abrogation of TLR4 and CD14 expression and signalling in human adrenocortical tumours. J Clin Endocrinol Metab. 2010;95:E421-9.
- Kanczkowski W, Chatzigeorgiou A, Samus M, Tran N, Zacharowski K, Chavakis T, Bornstein SR. Characterization of the LPS-induced inflammation of the adrenal gland in mice. Mol Cell Endocrinol. 2013;371:228-35.
- Kanczkowski W, Chatzigeorgiou A, Grossklaus S, Sprott D, Bornstein SR, Chavakis T. Role of the endothelial-derived endogenous anti-inflammatory factor Del-1 in inflammation-mediated adrenal gland dysfunction. Endocrinology. 2013;3:1181-9.
- Kanczkowski W, Alexaki VI, Grossklaus S, Popovic P, Tran N, Zacharowski K, Block NL, Chavakis T, Schally A Bornstein SR. Hypothalamo-pituitary and immune-mediated regulation of adrenal gland during systemic inflammation. Proc Natl Acad Sci U S A. 2013;110:14801-6.
- Kanczkowski W, Sue M, Zacharowski K, Reincke M, Bornstein SR. The role of adrenal gland microenvironment in the HPA axis function and dysfunction during sepsis. Mol Cell Endocrinol. 2015;408:241-248.
- Janewein C, Ngyuen T, Kanczkowski W, Heerdegen L, Kantharajah A, Dröse S, Bornstein SR, Scheller B and Zacharowski K. Mortality of septic mice strongly correlates with adrenal gland inflammation. Crit. Care Med. 2016;44:e190-9.
- Kanczkowski W, Sue M, Bornstein SR. Adrenal Gland Microenvironment and Its Involvement in the Regulation of Stress-Induced Hormone Secretion during Sepsis. Front Endocrinol (Lausanne). 2016 14;7:156.
- Kanczkowski W, Sue M, Bornstein SR. Adrenal Gland Microenvironment in health, disease and during regeneration. Hormone 2017 in press