15 research outputs found
Neisseria meningitidiselicits a pro-inflammatory response involving IÎşBÎś in a human blood-cerebrospinal fluid barrier model
Unpredictability of regression of analgesia during the continuous postoperative extradural infusion of bupivacaine.
The roles of acute and chronic pain in regression of sensory analgesia during continuous epidural bupivacaine infusion.
The impact of partial-oral endocarditis treatment on anxiety and depression in the POET trial
Two Distinctive Phenotypes of AcMNPV Display Different Immune Abilities and Intracellular Destiny
Neisseria meningitidis elicits a pro-inflammatory response involving IÎşBÎś in a human blood-cerebrospinal fluid barrier model
Background: The human-specific, Gram-negative bacterium Neisseria meningitidis (Nm) is a leading cause of bacterial meningitis worldwide. The blood-cerebrospinal fluid barrier (BCSFB), which is constituted by the epithelial cells of the choroid plexus (CP), has been suggested as one of the potential entry sites of Nm into the CSF and can contribute to the inflammatory response during infectious diseases of the brain. Toll-like receptors (TLRs) are involved in mediating signal transduction caused by the pathogens. Methods: Using a recently established in vitro model of the human BCSFB based on human malignant CP papilloma (HIBCPP) cells we investigated the cellular response of HIBCPP cells challenged with the meningitis-causing Nm strain, MC58, employing transcriptome and RT-PCR analysis, cytokine bead array, and enzyme-linked immunosorbent assay (ELISA). In comparison, we analyzed the answer to the closely related unencapsulated carrier isolate Nm Îą14. The presence of TLRs in HIBCPP and their role during signal transduction caused by Nm was studied by RT-PCR and the use of specific agonists and mutant bacteria. Results: We observed a stronger transcriptional response after infection with strain MC58, in particular with its capsule-deficient mutant MC58siaDâ, which correlated with bacterial invasion levels. Expression evaluation and Gene Set Enrichment Analysis pointed to a NFÎşB-mediated pro-inflammatory immune response involving up-regulation of the transcription factor IÎşBÎś. Infected cells secreted significant levels of pro-inflammatory chemokines and cytokines, including, among others, IL8, CXCL1-3, and the IÎşBÎś target gene product IL6. The expression profile of pattern recognition receptors in HIBCPP cells and the response to specific agonists indicates that TLR2/TLR6, rather than TLR4 or TLR2/TLR1, is involved in the cellular reaction following Nm infection. Conclusions: Our data show that Nm can initiate a pro-inflammatory response in human CP epithelial cells probably involving TLR2/TLR6 signaling and the transcriptional regulator IÎşBÎś
GWAS of bone size yields twelve loci that also affect height, BMD, osteoarthritis or fractures
Bone area is one measure of bone size that is easily derived from dual-energy X-ray absorptiometry (DXA) scans. In a GWA study of DXA bone area of the hip and lumbar spine (NââĽâ28,954), we find thirteen independent association signals at twelve loci that replicate in samples of European and East Asian descent (Nâ=â13,608 â 21,277). Eight DXA area loci associate with osteoarthritis, including rs143384 in GDF5 and a missense variant in COL11A1 (rs3753841). The strongest DXA area association is with rs11614913[T] in the microRNA MIR196A2 gene that associates with lumbar spine area (Pâ=â2.3âĂâ10â42, βâ=ââ0.090) and confers risk of hip fracture (Pâ=â1.0âĂâ10â8, ORâ=â1.11). We demonstrate that the risk allele is less efficient in repressing miR-196a-5p target genes. We also show that the DXA area measure contributes to the risk of hip fracture independent of bone density