Academic Journal
Optineurin deficiency contributes to impaired cytokine secretion and neutrophil recruitment in bacteria driven colitis.
| العنوان: | Optineurin deficiency contributes to impaired cytokine secretion and neutrophil recruitment in bacteria driven colitis. |
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| المؤلفون: | Chew, TS, O'Shea, NR, Sewell, GW, Oehlers, SH, Mulvey, CM, Crosier, PS, Godovac-Zimmermann, J, Bloom, SL, Smith, AM, Segal, AW |
| المصدر: | Disease Models & Mechanisms , 8 (8) 817- 829. (2015) |
| سنة النشر: | 2015 |
| المجموعة: | University College London: UCL Discovery |
| الوصف: | 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, we performed transcriptomic analysis in macrophages and identified a subgroup of CD patients with low expression of the autophagy receptor optineurin (OPTN). Here we clarified the role of OPTN deficiency in macrophage cytokine secretion, models of bacteria driven colitis and peritonitis in mice and zebrafish Salmonella infection. OPTN deficient bone-marrow derived macrophages (BMDM) stimulated with heat-killed E. coli secreted less proinflammatory TNF and IL6 cytokines despite similar gene transcription, which normalised with lysosomal and autophagy inhibitors suggesting that TNF is mistrafficked 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 with reduced levels of proinflammatory TNF in serum, diminished neutrophil recruitment to sites of acute inflammation and greater mortality. 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 may increase the risk of developing CD. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | text |
| اللغة: | English |
| Relation: | https://discovery.ucl.ac.uk/id/eprint/1470153/1/Dis.%20Model.%20Mech.-2015-Chew-817-29.pdf; https://discovery.ucl.ac.uk/id/eprint/1470153/ |
| الاتاحة: | https://discovery.ucl.ac.uk/id/eprint/1470153/1/Dis.%20Model.%20Mech.-2015-Chew-817-29.pdf https://discovery.ucl.ac.uk/id/eprint/1470153/ |
| Rights: | open |
| رقم الانضمام: | edsbas.C02984A0 |
| قاعدة البيانات: | BASE |
| الوصف غير متاح. |