(UL)
  • Vpliv inzulinu podobnega rastnega dejavnika-1 in endotelina-1 na izločanje vnetnih citokinov iz celic glije = The influence of insulin-like growth factor-1 and endothelin-1 on inflammatory cytokines secretion fom glial cells : Uniform Master's Study Programme Pharmacy
    Brišnik, Vita
    Insulin-like growth factor-1 exerts neuroprotective effects in various experimental models of ischemic stroke. Efficient treatments, that would benefit the majority of stroke patients, are lacking. ... Insulin-like growth factor-1 could be a good treatment option, due to its ability to interfere with many pathways in the ischemic cascade. Endothelin-1, a strong vasoconstrictor, is believed to be released from reactive astrocytes in multiple sclerosis patients and responsible for a reduction in cerebral blood flow, which may contribute to the pathology of multiple sclerosis. The endothelin-1 receptor antagonist bosentan increased the perfusion in the brain, so reduction of endothelin-1 levels in the brain could be beneficial for patients. The purpose of our study was to determine, whether insulin-like growth factor-1 modulates cytokine production by direct effects on microglia or astrocytes during neuroinflammation. Additionally, we wanted to find out, which side effects endothelin receptor antagonists may have on the neuroinflammation, by studying the effect of endothelin-1 on cytokine production. For our research we used the commercially available murine BV2 microglia and 1321N1 human astrocytic cell line. Western blot assays were used to detect functional IGF-1 receptors by assessing the phosphorylation of Akt and Erk kinases. The cells were exposed to a pro-inflammatory stimulus and treated with insulin-like growth factor-1, or they were pre-treated with endothelin-1, and later exposed to a pro-inflammatory stimulus. Cytokines released in the supernatant were measured by enzyme linked immunosorbent assay (ELISA), and the effects on the mRNA levels were assessed with real time quantitative polymerase chain reaction. Microglial BV2 cells express functional IGF-1 receptors signaling through the MAPK-pathway. After 5-hour incubation time with BV2 cells, insulin-like growth factor-1 significantly increased TNF-alpha production, when exposed to lipopolysaccharide, and significantly reduced TNF-alpha release, when exposed to interleukin-1?. After 24 h of pre-incubation with endothelin-1, BV2 cells secreted significantly less TNF-alpha in response to interleukin-1beta. We conclude, that insulin-like growth factor-1 modulates cytokine production and its pro- or anti-inflammatory effects depend on the type of stimulation. Therefore, additional studies should be done preferably in ischemic environment. Our results conclude, that endothelin-1 shows anti-inflammatory effect on neuroinflammation, but its cytotoxicity remains to be determined.
    Vrsta gradiva - magistrsko delo ; neleposlovje za odrasle
    Založništvo in izdelava - Ljubljana : [V. Brišnik], 2019
    Jezik - angleški
    COBISS.SI-ID - 4752497

    Povezava(-e):

    https://repozitorij.uni-lj.si/IzpisGradiva.php?id=108555

Knjižnica Signatura – lokacija, inventarna št. ... Status izvoda
Fakulteta za farmacijo, Ljubljana Knjižnica
emšf 576 BRIŠNIK VITA Vpliv 730
IN: 0016237 		prosto - za čitalnico
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