TitleInterleukin-1 mediated cell-type specific signaling in hippocampal neurons and astrocytes
NameHuang, Yangyang (author), Friedman, Wilma j (chair), Kim, Haesun (internal member), Jonakait, Mill (internal member), Jonakait, G Miller (internal member), Levison, Steve W (outside member), Rutgers University, Graduate School - Newark,
DescriptionInterleukin-1β (IL-1β) is a pro-inflammatory cytokine that is implicated in immune and inflammatory responses. In the central nervous system (CNS), IL-1β is synthesized and released during injury, infection, and many neurodegenerative diseases, but also under physiological conditions. Several IL-1-mediated signaling pathways and effects have been identified in hippocampal neurons and astrocytes, but their mechanisms have not been fully defined. IL-1 signaling requires the type one IL-1 receptor (IL-1RI) as well as IL-1 receptor accessory protein (IL-1RAcP) as a receptor partner. A novel isoform of the IL-1 receptor accessory protein, AcPb, has also been found in the CNS, but its role remains unclear. This thesis examined AcPb function in regulating IL-1β signaling. The results showed that IL-1β activated p38 MAPK but not NFκB in neurons. In astrocytes, IL-1β induced both p38 and NFκB pathways in regulating inflammatory responses. AcPb was not involved in mediating either p38 or NFκB in either cell type. In contrast, a physiological level of IL-1β treatment (0.01ng/ml) activated p-Src in neurons via AcPb in vitro. In addition, overexpression of AcPb in astrocytes was sufficient to induce p-Src mediated by IL-1β. Taken together, these results suggest that the restricted expression of AcPb in CNS neurons may mediate neuronal specific IL-1 pathways and outcomes, and that physiological and pathophysiological levels of IL-1β mediate particular neuronal functions via separate pathways.
NoteIncludes bibliographical references
Noteby Yangyang Huang
CollectionGraduate School - Newark Electronic Theses and Dissertations
Organization NameRutgers, The State University of New Jersey
RightsThe author owns the copyright to this work.