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Activin A und Follistatin bei bakteriellen Infektionen - Der Einfluss von Activin A auf Mikrogliazellen in vitro und der Einfluss von Follistatin auf den Verlauf einer E. coli-K1-Sepsis im Mausmodell
| Content Provider | Semantic Scholar |
|---|---|
| Author | Diesselberg, Catharina |
| Copyright Year | 2012 |
| Abstract | High concentrations of Activin A and Follistatin can be found in the cerebrospinal fluid (CSF) of patients with bacterial meningitis. Patients suffering from a sepsis have increased concentrations of Activin A and Follistatin in serum. In this study the effect of Activin A on microglial cells during infection was tested in vitro. Murine microglial cells were stimulated with Activin A 13 µg/ml, 13 ng/ml, 1.3 ng/ml and 0.13 ng/ml and co-stimulated with different TLR-agonists (P₃C 0.1 µg/ml, CpG 1 µg/ml, LPS 0.01 µg/ml). After stimulation, E. coli K1 1 x 10⁷ CFU/ml, a common meningitis pathogen, was added for 90 minutes. Afterwards the extracellular bacteria were killed with Gentamicin. Microglial cells were lysed with distilled water and the number of intracellular bacteria was determined with quantitative platting on blood agar plates. Activin A 13 ng/ml increased phagocytosis in combination with P₃C (p 0.05), effect on phagocytosis. In certain concentrations Activin A increased phagocytosis of microglial cells. Therefore Activin A or an analagon might be a new therapeutic option in future. The effect of Activin A on the release of TNF-α by microglial cells were tested with ELISA, but showed no meaningful effects. The influence of Activin A on the release of NO by microglial cells was tested in combination with P₃C 0.01 µg/ml, CpG 0.1 µg/ml and LPS 0.0003 µg/ml in the presence of IFN-γ. Activin A in combination with TLR-agonists increased the release of NO significantly (p < 0.001) compared to stimulated NO release of TLR-agonists only. Staining with Isolektin and Hamalaun showed that, Activin A changed the morphology of microglial cells from resting to activated. Testing Activin A with the WST/1 cell proliferation reagent, there was neither an evidence for changing the cell viability nor the density nor the cell toxity. In a mouse model of acute systemic inflammation induced by LPS it could be shown that the pre-administration of Follistatin increased survival (Jones et al. 2007). In this study we examined if FS also influences the course of disease in a mouse model with sepsis induced by an intraperitoneal injection of Escherichia coli K1 (E. coli K1), a Gram-negative bacterium frequently causing septic bacterial infections. 50 male, 3-month-old C57BL6/N mice were tested. The mice were weighted and their motor activity was tested with the tightrope test before and after infection. 24 mice were administered Follistatin 10 µg/ml intraperitoneal 30 minutes before infection. The 26 remaining mice of the control group received an intraperitoneal injection with 100 μl isotonic nonpyrogenic saline. The infection was induced with an intraperitoneal injection of E. coli K1 2x10⁵ CFU/ml. After death, bacterial concentrations in spleen and cerebellum were determined with quantitative platting. Follistatin did not have an influence on survival (p = 0.7065) or the resistance to bacterial infections. The weight loss and the motor activity did not differ between the two groups at any time (p > 0.05). In our mouse model we could not confirm the protective effect of FS observed during LPS-induced inflammation of an E. coli sepsis. |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | https://ediss.uni-goettingen.de/bitstream/handle/11858/00-1735-0000-000D-F012-1/diesselberg.pdf;jsessionid=AC375E25007ADDE8118C6AD8FCFA2447?sequence=4 |
| Language | English |
| Access Restriction | Open |
| Content Type | Text |
| Resource Type | Article |
