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| Title |
Η έκφραση και η λειτουργία του ομοιοστατικού μορίου Del-1 κατα τη σήψη στη νεογνική ηλικία |
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Author
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Δανοπούλου, Μαρία Άννα
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Thesis advisor
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Χανιωτάκης, Νικόλαος
Τσατσάνης, Χρήστος
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| Abstract |
Sepsis remains a severe systemic response to bacterial infection, causing significant morbidity and mortality in all age groups, especially in immunocompromised hosts and newborns. Del-1 (developmental endothelial locus-1) is a soluble anti¬inflammatory protein secreted from endothelium that inhibits leukocyte's ability to phagocytose and adhere to blood vessels, preventing their transmigration from blood stream to tissues. Newborns are in high risk of mortality in case of bacterial infection because Del-1 levels are higher contrary to adults.
In this study, we investigated the levels of Del-1 protein expression in human neonates, similarly to murines, and shown that they have higher serum Del-1 levels compared to children or adults. The contribution of Del-1 in the outcome of sepsis was determined in animal models. Wild type (WT) and Del-1 deficient neonatal mice were subjected to sepsis and at several time points after infection, inflammatory response and survival rates were determined.
The concentration of Del-1 protein was measured with human serum of adults, neonates, healthy and patients with Systemic Inflammatory Response Syndrome (SIRS) and the results shown that the concentration of Del-1 is higher in neonates contrary to adults. The concentration of several cytokines such as IL-6 and IL-10 were measured and correlated with Del-1 protein levels.
To investigate whether Del-1 inhibition can be exploited therapeutically to improve survival from neonatal sepsis, WT mice were treated with human recombinant IL-10. The results showed that Del-1 expression levels were decreased contrary to normal expression levels.
Our pre-clinical study highlights the role of Del-1 as a negative prognostic factor in neonatal sepsis and address the efficacy of Del-1 inhibition as a novel therapeutic strategy in sepsis.
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| Language |
Greek |
| Issue date |
2018-11-30 |
| Collection
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School/Department--School of Sciences and Engineering--Department of Chemistry--Graduate theses
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Type of Work--Graduate theses
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| Permanent Link |
https://elocus.lib.uoc.gr//dlib/d/b/4/metadata-dlib-1547451024-171551-16184.tkl
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| Views |
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