Project description:Bullous pemphigoid (BP) is the most common autoimmune skin blistering disease characterized by autoimmunity against the hemidesmosomal proteins BP180, type XVII collagen, and BP230. To elucidate the genetic basis of susceptibility to BP, we performed the first genome-wide association study (GWAS) in Germans. This GWAS was combined with HLA locus targeted sequencing in an additional independent BP cohort. The strongest association with BP in Germans tested in this study was observed in the two HLA loci, HLA-DQA1*05:05 and HLA-DRB1*07:01. Further studies with increased sample sizes and complex studies integrating multiple pathogenic drivers will be conducted.
Project description:The study of the immunoskeletal interface has led to the discovery of numerous cytokines involved in the regulation of bone remodeling, providing valuable information on the pathogenesis of osteoporosis. The role of inflammatory cytokines of the Th1 and Th17 profile in osteoporosis is well known. Here we focus on two newly discovered Th2 cytokines, IL-31 and IL-33, whose implications in osteoporosis are recently emerging. Clinical and experimental observations suggest an important role of the IL-33/IL-31 axis in osteoporosis. IL-33 induces IL-31 secretion by Th2 cells and inhibits RANKL-dependent osteoclastogenesis, thus counteracting bone loss. IL-31 influences Th1/Th17 osteoclastogenetic inflammation and limits Th2 osteoprotective processes, thus favoring osteoporosis. Better knowledge of the role of IL-31 and IL-33 and their receptor complexes in osteoporosis could provide an interesting perspective for the development of new and more effective therapies, possibly with less side effects.
Project description:Cytokines play an important role in the regulation of the immune system (adaptive and innate). Given their importance in proinflammatory processes, cytokines have been used for understanding the pathogenesis and as biomarkers in many diseases. IL-31 and IL-33 are still considered novel cytokines. IL-31 controls signalling and regulates a huge amount of biological functions: it induces proinflammatory cytokines, regulates cell proliferation, and is involved also in tissue remodelling. On the other hand, IL-33 has been identified as an "alarmin" released from the epithelial cells and from different human tissues and organs after a damage following, that is, an inflammatory process. The aim of this literature review is to strengthen the hypothesis about an IL-31/IL-33 axis by evaluating the most recent studies linking these two cytokines. Literature data showed that, in many cases, IL-31 and IL-33 are linked to each other and that their expression is correlated with disease severity. The presence of one interleukin might stimulate the induction of the other, amplifying inflammation and the consequent detrimental processes. In a near future, influencing their balance could be helpful in modulating the first responses of the immune system in order to prevent the development of many inflammation-related diseases.
Project description:Oleanolic acid significantly inhibited neurosphere formation in a dose-dependent manner, and achieved a maximum effect at 10 nM. OA also reduced the 5-ethynyl-2’-deoxyuridine (EdU) incorporation into NSCs, indicating an inhibition on proliferation of NSCs. Next, in western blotting analysis, the protein expression of neuron-specific marker tubulin-βⅢ (TuJ1) and Mash1 was increased, while the astrocyte-specific marker glial fibrillary acidic protein (GFAP) decreased. In immunofluorescence analysis, OA significantly elevated the percentage of TuJ1-positive cells and reduced GFAP-positive cells. Using DNA microarrays, 183 genes were found to be differentially regulated by OA.
Project description:Oleanolic acid significantly inhibited neurosphere formation in a dose-dependent manner, and achieved a maximum effect at 10 nM. OA also reduced the 5-ethynyl-2M-bM-^@M-^Y-deoxyuridine (EdU) incorporation into NSCs, indicating an inhibition on proliferation of NSCs. Next, in western blotting analysis, the protein expression of neuron-specific marker tubulin-M-NM-2M-bM-^EM-" (TuJ1) and Mash1 was increased, while the astrocyte-specific marker glial fibrillary acidic protein (GFAP) decreased. In immunofluorescence analysis, OA significantly elevated the percentage of TuJ1-positive cells and reduced GFAP-positive cells. Using DNA microarrays, 183 genes were found to be differentially regulated by OA. Neural stem cells derived form mouse embrynic brains were treated with Oleanolic acid or not. Each group had 4 biological relicates each from a mouse.