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10.1242/dmm.020362 http://scihub22266oqcxt.onion/10.1242/dmm.020362 26044960!4527293!26044960     free     free     free Warning: file_get_contents(https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=26044960&cmd=llinks): Failed to open stream: HTTP request failed! 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Optineurin deficiency in mice contributes to impaired cytokine secretion and neutrophil recruitment in bacteria-driven colitis |pdf=|usr=}}{{26044960}} gab.com Text Optineurin deficiency in mice contributes to impaired cytokine secretion and neutrophil recruitment in bacteria-driven colitis JO: Dis Model Mech http://www.kidney.de/pget.php?&tw=1&pmid=26044960 #FOAvip Crohn's disease (CD) is associated with delayed neutrophil recruitment and bacterial clearance at sites of acute inflammation as a result of impaired secretion of proinflammatory cytokines by macrophages. To investigate the impaired cytokine secretion and confirm our previous findings, we performed transcriptomic analysis in macrophages and identified a subgroup of individuals with CD who had low expression of the autophagy receptor optineurin (OPTN). We then clarified the role of OPTN deficiency in: macrophage cytokine secretion; mouse models of bacteria-driven colitis and peritonitis; and zebrafish Salmonella infection. OPTN-deficient bone-marrow-derived macrophages (BMDMs) stimulated with heat-killed Escherichia coli secreted less proinflammatory TNFalpha and IL6 cytokines despite similar gene transcription, which normalised with lysosomal and autophagy inhibitors, suggesting that TNFalpha is mis-trafficked to lysosomes via bafilomycin-A-dependent pathways in the absence of OPTN. OPTN-deficient mice were more susceptible to Citrobacter colitis and E. coli peritonitis, and showed reduced levels of proinflammatory TNFalpha in serum, diminished neutrophil recruitment to sites of acute inflammation and greater mortality, compared with wild-type mice. Optn-knockdown zebrafish infected with Salmonella also had higher mortality. OPTN plays a role in acute inflammation and neutrophil recruitment, potentially via defective macrophage proinflammatory cytokine secretion, which suggests that diminished OPTN expression in humans might increase the risk of developing CD. Twit Text FOAVip Optineurin deficiency in mice contributes to impaired cytokine secretion and neutrophil recruitment in bacteria-driven colitis ????Dis Model Mech http://www.kidney.de/pget.php?&tw=1&pmid=26044960 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=26044960 #FOAvip English Wikipedia <ref>{{Cite pmid|26044960}}</ref> Optineurin deficiency in mice contributes to impaired cytokine secretion and neutrophil recruitment in bacteria-driven colitis #MMPMID26044960 Chew TS; O'Shea NR; Sewell GW; Oehlers SH; Mulvey CM; Crosier PS; Godovac-Zimmermann J; Bloom SL; Smith AM; Segal AW Dis Model Mech 2015[Aug]; 8 (8): 817-29 PMID26044960show ga Crohn's disease (CD) is associated with delayed neutrophil recruitment and bacterial clearance at sites of acute inflammation as a result of impaired secretion of proinflammatory cytokines by macrophages. To investigate the impaired cytokine secretion and confirm our previous findings, we performed transcriptomic analysis in macrophages and identified a subgroup of individuals with CD who had low expression of the autophagy receptor optineurin (OPTN). We then clarified the role of OPTN deficiency in: macrophage cytokine secretion; mouse models of bacteria-driven colitis and peritonitis; and zebrafish Salmonella infection. OPTN-deficient bone-marrow-derived macrophages (BMDMs) stimulated with heat-killed Escherichia coli secreted less proinflammatory TNFalpha and IL6 cytokines despite similar gene transcription, which normalised with lysosomal and autophagy inhibitors, suggesting that TNFalpha is mis-trafficked to lysosomes via bafilomycin-A-dependent pathways in the absence of OPTN. OPTN-deficient mice were more susceptible to Citrobacter colitis and E. coli peritonitis, and showed reduced levels of proinflammatory TNFalpha in serum, diminished neutrophil recruitment to sites of acute inflammation and greater mortality, compared with wild-type mice. Optn-knockdown zebrafish infected with Salmonella also had higher mortality. OPTN plays a role in acute inflammation and neutrophil recruitment, potentially via defective macrophage proinflammatory cytokine secretion, which suggests that diminished OPTN expression in humans might increase the risk of developing CD. |*Neutrophil Infiltration[MESH] |Adult[MESH] |Animals[MESH] |Bacteria/*metabolism[MESH] |Case-Control Studies[MESH] |Cell Cycle Proteins[MESH] |Citrobacter/physiology[MESH] |Colitis/blood/microbiology/pathology[MESH] |Crohn Disease/genetics/microbiology[MESH] |Cytokines/blood/*metabolism[MESH] |Escherichia coli Infections/prevention & control[MESH] |Escherichia coli/physiology[MESH] |Eye Proteins/*metabolism[MESH] |Female[MESH] |Golgi Apparatus/metabolism[MESH] |Humans[MESH] |Inflammation Mediators/metabolism[MESH] |Inheritance Patterns/genetics[MESH] |Macrophages/metabolism[MESH] |Male[MESH] |Membrane Transport Proteins[MESH] |Mice[MESH] |Middle Aged[MESH] |Models, Biological[MESH] |Polymorphism, Single Nucleotide/genetics[MESH] |Transcription Factor TFIIIA/deficiency/metabolism[MESH] |Tumor Necrosis Factor-alpha/metabolism[MESH] |Up-Regulation[MESH]Optineurin deficiency in mice contributes to impaired cytokine secreti(epmc).pdf DeepDyve Pubget Overpricing