Signaling pathways involved in IL-1beta-induced regulation of MOR expression in human neurons
Abstract
Scope and Method of Study: The scope of this thesis was to study the effects of pro-inflammatory cytokine, IL-1B on the expression of MOR in SK-N-SH neurons in vitro. Used real-time PCR to measure changes in mRNA expression of MOR and immunocytochemistry (ICC) to see changes in MOR proteins levels as captured using Confocal microscopy. Findings and Conclusions: Our finding concluded an IL-1B-dependent up regulation of MOR expression at both the mRNA and protein levels. Also, the effects of IL-1B on MOR expression were measured to be more robust than that induced by morphine, implicating a signaling pathway dependent process. Further studies using signaling inhibitors alluded to the role of MEK1/2 and p38 MAPK in the regulation of MOR expression following morphine treatment and an NF-xB-dependent mechanism for the regulation of MOR expression following IL-1B treatment. Further studies to elucidate the precise role of IL-1B on the expression of MORs would be multiple-modal: 1 - primary CNS cell culture; 2 - primary CNS/microglia cell culture; 3 - neuroinflammatory, in vivo studies; 4 - measure cytokines released in response morphine administration, measure changes in mRNA and protein levels of MOR in the CNS of in vivo models; 5 - elucidate the role of microRNAs on the expression of MOR mRNA. Overall, the relationship between the immune mediators such as IL-1B and the genes exclusively expressed in the CNS such as opioid receptor is complex and multimodal. Our study discovered and supported novel findings, such as the expression of IL-1RI in human Neuroblastoma cells and IL-1B ability to out-compete the regulation of MOR expression by morphine. Results from these IL-1B-morphine competition studies have opened new avenues for discovery, which would help answer why IL-1B had a more robust and "faster" affect on MOR expression.
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- OSU Dissertations [11222]