N-3 PUFAs induce inflammatory tolerance by formation of KEAP1-containing SQSTM1/p62-bodies and activation of NFE2L2
| العنوان: | N-3 PUFAs induce inflammatory tolerance by formation of KEAP1-containing SQSTM1/p62-bodies and activation of NFE2L2 |
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| المؤلفون: | Ida Johansson, Jan Kristian Damås, Ismail Sergin, Babak Razani, Geir Bjørkøy, Trude Helen Flo, Eli Kjøbli, Jennifer Mildenberger |
| المصدر: | Autophagy |
| بيانات النشر: | Taylor & Francis, 2017. |
| سنة النشر: | 2017 |
| مصطلحات موضوعية: | 0301 basic medicine, TNF, MDM, Mice, STAT1, Sequestosome-1 Protein, SQSTM1, TLR4, IKBKB, Cells, Cultured, NFE2L2, Inclusion Bodies, Mice, Knockout, education.field_of_study, Kelch-Like ECH-Associated Protein 1, CXCL10, p62, Basic Research Paper, DHA, Biochemistry, Docosahexaenoic acid, Tumor necrosis factor alpha, omega-3, Inflammation Mediators, Transcriptional Activation, LPS, NF-E2-Related Factor 2, Biology, 03 medical and health sciences, Sequestosome 1, Fatty Acids, Omega-3, Autophagy, Animals, education, Molecular Biology, OA, Inflammation, Binding protein, Macrophages, IRF1, Cell Biology, IRF3, KEAP1, ALIS, NFKB, 030104 developmental biology, aggregates, IP10, PUFA |
| الوصف: | Inflammation is crucial in the defense against infections but must be tightly controlled to limit detrimental hyperactivation. Our diet influences inflammatory processes and omega-3 polyunsaturated fatty acids (n-3 PUFAs) have known anti-inflammatory effects. The balance of pro- and anti-inflammatory processes is coordinated by macrophages and macroautophagy/autophagy has recently emerged as a cellular process that dampens inflammation. Here we report that the n-3 PUFA docosahexaenoic acid (DHA) transiently induces cytosolic speckles of the autophagic receptor SQSTM1/p62 (sequestosome 1) (described as SQSTM1/p62-bodies) in macrophages. We suggest that the formation of SQSTM1/p62-bodies represents a fast mechanism of NFE2L2/Nrf2 (nuclear factor, erythroid 2 like 2) activation by recruitment of KEAP1 (kelch like ECH associated protein 1). Further, the autophagy receptor TAX1BP1 (Tax1 binding protein 1) and ubiquitin-editing enzyme TNFAIP3/A20 (TNF α induced protein 3) could be identified in DHA-induced SQSTM1/p62-bodies. Simultaneously, DHA strongly dampened the induction of pro-inflammatory genes including CXCL10 (C-X-C motif chemokine ligand 10) and we suggest that formation of SQSTM1/p62-bodies and activation of NFE2L2 leads to tolerance towards selective inflammatory stimuli. Finally, reduced CXCL10 levels were related to the improved clinical outcome in n-3 PUFA-supplemented heart-transplant patients and we propose CXCL10 as a robust marker for the clinical benefits mobilized by n-3 PUFA supplementation. © 2017 Jennifer Mildenberger, Ida Johansson, Ismail Sergin, Eli Kjøbli, Jan Kristian Dama s, Babak Razani, Trude Helen Flo, and Geir Bjørkøy. Published with license by Taylor & Francis This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License (http://creativecommons.org/licenses/by-nc-nd/4.0Test/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited, and is not altered, transformed, or built upon in any way. |
| اللغة: | English |
| تدمد: | 1554-8635 1554-8627 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d9623da87ae32155a5736b24f5c406ddTest http://europepmc.org/articles/PMC5640206Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....d9623da87ae32155a5736b24f5c406dd |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15548635 15548627 |
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