The induction and effects of Substance P and its receptor in human immune cells and neurons : potential relevance in multiple sclerosis

摘要: INTRODUCTION: Substance P (SP) has well-established roles in neurogenic inflammation and pain transmission, however recently, a number of SP immunomodulatory effects have been shown. In this thesis its neurokinin-1-receptor (NK1R) role autoimmune was investigated with an applicability to multiple sclerosis (MS). the four experimental chapters receptor studied human immune cells neurons focus on relationship Th17 Th1 pathways as main pro-inflammatory arms pathology. AIMS: To quantify inflammatory cytokine induction peripheral blood mononuclear (PBMC); measure pathway NK1R expression T NT2 neurons; compare relevant parameters relapsing-remitting MS patients healthy controls. METHODS: Real-time PCR, flow cytometry, ELISA, Western blotting promoter studies were used target genes under different stimulation conditions. Cells isolated from consented controls, patients, or differentiated specified. RESULTS: PBMC, treatment significantly increased relative quantity IL-12/IL-23 subunit p40, IL-23 p19 IL-12 p35 mRNA showing that can signal IL-23. As part reciprocal mechanism cells, strongly upregulated by cytokines less cytokines. These for confirmed at protein levels. The prevalent earlier stages compared effects. novel finding, IL-17 (IL-17A) had direct via functionally expressed receptor. Neuronal mRNA-level subject regulation IL-17, whereas precursor considerably IL-17. relapse downregulated controls. This finding is likely associated activity acute relapse. CONCLUSIONS: Mutual interactions exist between Th17, responses involvement supports mediating occurs relapse. results also show neuronal involving pathway.