Integrating the hypoxia and adrenergic responses in the adrenal gland in systemic inflammation

Principal Investigators

Prof. Dr. med. Ali El-Armouche
ali.el-armouche(at)tu-dresden.de
Institute of Pharmacology and Toxicology
University Hospital Carl Gustav
Technische Universität Dresden

Prof. PhD Ben Wielockx
ben.wielockx(at)tu-dresden.de
Institute of Clinical Chemistry and Laboratory Medicine
Clinical Pathobiochemistry
University Hospital Carl Gustav Carus
Technische Universität Dresden

Prof. Dr. med. Triantafyllos Chavakis
triantafyllos.chavakis(at)uniklinikum-dresden.de
Institute of Clinical Chemistry and Laboratory Medicine
University Hospital Carl Gustav Carus Dresden
Technische Universität Dresden

Scientific Staff

Tatyana Grinenko (Postdoc)
Deepika Watts (Postdoc)
Silvio Weber (Postdoc)
Marta Murray (PhD)
Sundary Sormendi (PhD)

Project Description

Project A02 deals with the role of the adrenal gland and its secretion of hormones while coping with critical illness such as acute inflammatory reactions. As the adrenal gland is both a target and a regulator of this immune response, the project aims to understand the link between the hypoxia pathway, with low oxygen, within the adrenal gland and the adrenergic system and their effect on the innate immune response. Ultimately this might prove beneficial also in limiting the excessive or sustained pro-inflammatory activity in systemic infection.

Aims

(I) Characterise in depth the role of systemic hypoxia on the adrenal gland and its immunemodulatory effect during systemic inflammatory response syndrome (SIRS) in mice.
(II) Determine the consequences of ablating central hypoxia proteins in cells of the adrenal medulla and/or cortex and its effect during endotoxemia.
(III) Define the potential regulatory function of adrenergic receptor β2AR on monocytes/ macrophages during systemic inflammation, its feedback to the adrenal gland and its regulation through PHD3.

Publications

1- Watts, D., Stein, J., Meneses, A., Bechmann, N., Neuwirth, A., Kaden, D., Krüger, A., Sinha, A., Alexaki, V. I., Perez-Rivas, L. G., Kircher, S., Martinez, A., Theodoropoulou, M., Eisenhofer, G., Peitzsch, M., El-Armouche, A., Chavakis, T., and Wielockx, B. (2020) HIF1α is an essential regulator of steroidogenesis in the adrenal gland. bioRxivdoi.org/ 10.1101/2020.07.08.1917832.         

2- Watts, D., Bechmann, N., Meneses, A., Poutakidou, I. K., Kaden, D., Conrad, C., Krüger, A., Stein, J., El-Armouche, A., Chavakis, T., Eisenhofer, G., Peitzsch, M., and Wielockx, B. (2020) Hypoxia pathway proteins regulate the synthesis and release of epinephrine in the mouse adrenal gland. bioRxiv doi.org/ 10.1101/2020.10.15.3409433.         

3- Watts, D., Gaete, D., Rodriguez, D., Hoogewijs, D., Rauner, M., Sormendi, S., and Wielockx, B. (2020) Hypoxia Pathway Proteins are Master Regulators of Erythropoiesis. Int J Mol Sci214.        

4- Sormendi, S., Deygas, M., Sinha, A., Krüger, A., Kourtzelis, I., Le Lay, G., Bernard, M., Sáez, P. J., Gerlach, M., Franke, K., Meneses, A., Kräter, M., Palladini, A., Guck, J., Coskun, Ü., Chavakis, T., Vargas, P., and Wielockx, B.(2020) HIF2α is a Direct Regulator of Neutrophil Motility. bioRxiv doi.org/ 10.1101/2020.06.05.1371335.        

5- Saadatmand, A. R., Sramek, V., Weber, S., Finke, D., Dewenter, M., Sticht, C., Gretz, N., Wustemann, T., Hagenmueller, M., Kuenzel, S. R., Meyer-Roxlau, S., Kramer, M., Sossalla, S., Lehmann, L. H., Kammerer, S., Backs, J., and El-Armouche, A. (2019) CaM kinase II regulates cardiac hemoglobin expression through histone phosphorylation upon sympathetic activation. Proc Natl Acad Sci U S A116, 22282-22287 6.         

6- Wielockx, B., Grinenko, T., Mirtschink, P., and Chavakis, T. (2019) Hypoxia Pathway Proteins in Normal and Malignant Hematopoiesis. Cells 8 

7- Singh, R. P., Grinenko, T., Ramasz, B., Franke, K., Lesche, M., Dahl, A., Gassmann, M., Chavakis, T., Henry, I., and Wielockx, B. (2018) Hematopoietic Stem Cells but Not Multipotent Progenitors Drive Erythropoiesis during Chronic Erythroid Stress in EPO Transgenic Mice. Stem cell reports10, 1908-1919 8.        

8- Kiers, D., Wielockx, B., Peters, E., van Eijk, L. T., Gerretsen, J., John, A., Janssen, E., Groeneveld, R., Peters, M., Damen, L., Meneses, A. M., Kruger, A., Langereis, J. D., Zomer, A. L., Blackburn, M. R., Joosten, L. A., Netea, M. G., Riksen, N. P., van der Hoeven, J. G., Scheffer, G. J., Eltzschig, H. K., Pickkers, P., and Kox, M. (2018) Short-Term Hypoxia Dampens Inflammation in vivo via Enhanced Adenosine Release and Adenosine 2B Receptor Stimulation. EBioMedicine33, 144-156