2007). There is some debate in the literature whether the more recent variant induces more severe clinical signs. The prevalence and genetic characteristics of the three antigenic variants varies over time with distinct populations found in different geographic regions. The most recently published study characterising CPV-2 viruses in the UK dates back to 2008, where only CPV-2a and CPV-2b strains were identified (Davies 2008). We would like to raise awareness of our current study, which aims to characterise which CPV strains are now present within the UK. The study is supported by Petplan Charitable Trust funding and a BSAVA PetSavers undergraduate bursary. We would encourage colleagues to submit faeces samples to us from dogs with confirmed or suspected CPV. These will be subject to PCR and sequencing to determine strain type and understand virus evolution. We aim to correlate sequence data with factors such as signalment, disease severity or geographical location. We would be happy to discuss the study with interested colleagues and arrange to supply collection pots, prepaid envelopes and further information about the project.
lymphoid tissue and alveolar macrophages. IPF patient lung section analysis revealed an absence of TRAIL expression compared to controls. IPF patients had significantly lower serum levels of TRAIL than controls which inversely correlated with TLCO (% predicted) and positively correlated with survival from diagnosis. Conclusions We demonstrated that the neutrophilic inflammatory response to bleomycin is increased in TRAILÀ/À compared with wild-type mice and that this finding is associated with increased collagen deposition. We also demonstrated reduced pulmonary and systemic expression of TRAIL in IPF, which correlates with worse pulmonary function and clinical outcome. This data suggests TRAIL may have biomarker potential and therapeutic benefit in pulmonary fibrosis. The pleiotropic cytokine TNFa plays a key role in the pathogenesis of many chronic inflammatory lung diseases, particularly sarcoidosis, asthma and COPD. Due to its broad spectrum of activity however, current anti-TNFa therapies are of limited efficacy in these conditions and are associated with an increased risk of infection and malignancy. Interaction of TNFa with its cognate receptor, TNF-R1 initiates a signalling cascade that leads ultimately to the phosphorylation of the transcription factor NF-kB. This allows NF-kB to shuttle in a co-ordinated manner between the cytoplasm and the nucleus, leading to the up-regulation of genes that are key to cellular inflammatory and apoptotic responses. We propose that the novel TNF-R1 interacting protein TRUSS (TNF-R1 Ubiquitous Scaffolding and Signalling protein), which interacts with members of the TNF-R1 signalling cascade, may regulate this process. A549 cells, which express high levels of endogenous TRUSS, were transfected transiently with siRNA, which resulted in 80614% (mean6SEM, n¼16) knockdown of TRUSS mRNA. TRUSS deficient cells demonstrated a profound early (<1 h) defect in the nuclear translocation of p50/p65 subunits following TNFa stimulation (p<0.05, n¼3). As a consequence, in the absence of TRUSS, p50, its precursor phospho-p105, and phospho-p65 were retained in the cytoplasm in these cells following TNFa stimulation. Furthermore, TRUSS depletion caused a reduction in TNFa stimulated NF-kB (p<0.01, n¼7) and AP-1 (p<0.01, n¼6) luciferase reporter activity; this was associated with a decrease in interleukin 6, RANTES, G-CSF and GM-CSF (p<0.05, n¼6) mRNA and protein expression while MCP-1, CXCL5 and IL-8 were not affected. Although TRUSS deplete cells displayed impaired up-regulation of IkBa mRNA in response to TNFa stimulation, the protein response was intact. Upstream signalling molecules TNFR1, TRADD, TRAF2 and RIP were unaffected by TRUSS knockdown. In conclusion, these data suggest a novel role for TRUSS as a scaffold protein involved in the initial nuclear translocation of p50/p65 NF-kB subunits, which regulates the early pro-inflammatory response to TNFa. Hence TRUSS may represent a more selective therapeutic target for modulating TNFa functions. S112 TNF-R1 UBIQUITOUS SCAFFOLDING AND SI...
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