| dc.contributor.advisor | Reichardt, Holger Prof. Dr. | |
| dc.contributor.author | Amouret, Agathe | |
| dc.date.accessioned | 2023-01-10T15:13:34Z | |
| dc.date.available | 2023-01-17T00:50:10Z | |
| dc.date.issued | 2023-01-10 | |
| dc.identifier.uri | http://resolver.sub.uni-goettingen.de/purl?ediss-11858/14444 | |
| dc.identifier.uri | http://dx.doi.org/10.53846/goediss-9645 | |
| dc.format.extent | 135 Seiten | de |
| dc.language.iso | eng | de |
| dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | |
| dc.subject.ddc | 610 | |
| dc.title | Novel therapeutic approaches to treat inflammatory conditions with glucocorticoid and calciferol nanoparticles in vivo and in vitro | de |
| dc.type | doctoralThesis | de |
| dc.contributor.referee | Walter, Lutz Prof. Dr. | |
| dc.date.examination | 2022-10-27 | de |
| dc.description.abstracteng | The body is constantly confronted with environmental threats and sometimes the
entry of pathogens leads to severe inflammatory conditions such as sepsis or acute
lung injury (ALI). Both diseases are characterized by a dysregulated immune system,
which compromises homeostasis and induces multiple organ failure, thus being
potentially lethal. While pathophysiological changes in ALI are mostly confined to the
lung, sepsis is an example of a systemic inflammation affecting different organs
including spleen, liver and lung. GCs are used in both conditionsto reduce the so called
“cytokine storm”, but high doses of GCs may also aggravate lymphocytopenia
occurring in both diseases, leading to a severe risk of secondary infections and poorer
outcome. Targeting specific cell types in GC treatment could allow to overcome this
side effect as nanoparticles were shown to be mainly taken up by macrophages. Our
results revealed that free synthetic GCs and GC-containing nanoparticles efficiently
reduced the pro-inflammatory profile and tissue damage in a mouse model of sepsis.
However, in contrast to free GCs, a tendency was observed that using nanoparticles
prevented a further aggravation of lymphocytopenia. Nonetheless, the therapeutic
efficacy of both GC formulations was similar in sepsis as well as ALI mouse models.
Interestingly, the analysis of human peripheral blood monocytes also unveiled a novel
function of GCs in regulating the energy metabolism of myeloid cells in inflammatory
conditions. Finally, nanoparticles containing calcitriol, the active form of vitamin D,
were characterized as a potential alternative to GCs in sepsis or ALI therapy allowing
to avoid side-effects of high doses of calcitriol. Our results show a good anti-
inflammatory effect of newly formulated calcitriol nanoparticles, which were
efficiently engulfed by macrophages and fibroblasts in a clathrin-dependent manner
before being localized to the lysosomal compartment. Collectively, the use of
nanoparticles offers interesting new possibilities for the treatment of inflammatory
conditions with the potential to reduce adverse effects of GCs and calcitriol. | de |
| dc.contributor.coReferee | Odoardi, Francesca Prof. Dr. | |
| dc.contributor.thirdReferee | Lüder, Carsten Prof. Dr. | |
| dc.contributor.thirdReferee | Dressel, Ralf Prof. Dr. | |
| dc.contributor.thirdReferee | Meyer, Thomas Prof. Dr. | |
| dc.subject.ger | Sepsis | de |
| dc.subject.ger | Acute Lung Injury (ALI) | de |
| dc.subject.ger | Nanoparticles | de |
| dc.subject.ger | Glucocorticoids | de |
| dc.subject.ger | Calciferol | de |
| dc.subject.eng | Sepsis | de |
| dc.subject.eng | Acute Lung Injury (ALI) | de |
| dc.subject.eng | Glucocorticoids | de |
| dc.subject.eng | Calciferol | de |
| dc.subject.eng | Nanoparticles | de |
| dc.identifier.urn | urn:nbn:de:gbv:7-ediss-14444-3 | |
| dc.affiliation.institute | Medizinische Fakultät | |
| dc.subject.gokfull | Medizin (PPN619874732) | de |
| dc.description.embargoed | 2023-01-17 | de |
| dc.identifier.ppn | 183072326X | |
| dc.notes.confirmationsent | Confirmation sent 2023-01-11T06:15:01 | de |