Macrophages Down-Regulate Gene Expression of Intervertebral Disc Degenerative Markers Under a Pro-inflammatory Microenvironment
| العنوان: | Macrophages Down-Regulate Gene Expression of Intervertebral Disc Degenerative Markers Under a Pro-inflammatory Microenvironment |
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| المؤلفون: | Ana J. Silva, Joana R. Ferreira, Carla Cunha, João V. Corte-Real, Mafalda Bessa-Gonçalves, Mario A. Barbosa, Susana G. Santos, Raquel M. Gonçalves |
| المساهمون: | Instituto de Investigação e Inovação em Saúde |
| المصدر: | Frontiers in Immunology Frontiers in Immunology, Vol 10 (2019) |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | Down-Regulation / immunology, 0301 basic medicine, MMP3, Intervertebral Disc Degeneration / pathology, medicine.medical_treatment, Cell, C-C chemokine receptor type 7, Inflammation / immunology, Intervertebral Disc Degeneration, intervertebal disc, Cellular Microenvironment / immunology, Inflammation / pathology, Macrophages / immunology, Organ culture, Macrophages / pathology, 0302 clinical medicine, Immunology and Allergy, Cytokines / immunology, Original Research, Intervertebal disc, musculoskeletal system, Cell biology, medicine.anatomical_structure, Cytokine, Cellular Microenvironment, Cytokines, medicine.symptom, ex vivo model, Ex vivo model, lcsh:Immunologic diseases. Allergy, musculoskeletal diseases, Immunology, Down-Regulation, Inflammation, tissue regeneration, Biology, 03 medical and health sciences, organ culture, Immune system, Downregulation and upregulation, medicine, Animals, Humans, Aggrecan, Macrophages, Intervertebral Disc Degeneration / immunology, 030104 developmental biology, Tissue regeneration, Cattle, lcsh:RC581-607, 030215 immunology |
| الوصف: | Low back pain is a highly prevalent clinical problem and intervertebral disc (IVD) degeneration is now accepted as the major pathophysiological mechanism responsible for this condition. Accumulating evidence suggests that inflammation plays a crucial role in the progression of human IVD degeneration, with macrophages being pointed as the key immune cell players in this process since their infiltration in degenerated IVD samples has been extensively demonstrated. Since they are highly plastic, macrophages can play different roles depending on the microenvironmental cues. The study of inflammation associated with IVD degeneration has been somehow neglected and one of the reasons is related with lack of adequate models. To overcome this, we established and characterized a new model of IVD organ culture under proinflammatory conditions to further dissect the role of macrophages in IVD associated immune response. For that, human monocyte-derived macrophages were co-cultured either with bovine caudal IVD punches in the presence of the pro-inflammatory cytokine IL-1ß, or IVD-conditioned medium (CM), to investigate how IVD-produced factors influence macrophage phenotype. After 72 h, metabolic activity, gene expression and cytokine profile of macrophages and IVD cells were measured. Our results show that macrophages and IVDs remain metabolically active in the presence of IL-1ß, significantly upregulate CCR7 gene expression and increase production of IL-6 on macrophages. When treating macrophages with IL-1ß-IVD-CM, CCR7 upregulation follows the same trend, while for IL-6 an opposite effect was observed. On the other hand, macrophages interfere with IVD ECM remodeling, decreasing MMP3 expression and downregulating aggrecan and collagen II gene expression in the presence of IL-1ß. Overall, the co-culture model established in this study can be considered a suitable approach to address the cellular and molecular pathways that regulate macrophage-IVD crosstalk, suggesting that degenerated IVD tissue tends to polarize human macrophages toward a more proinflammatory profile, which seems to aggravate IVD degeneration. This model could be used to improve the knowledge of the mechanisms that link IVD degeneration and the immune response. This work was financed by European Union funds through Bioengineered Therapies for infectious diseases and tissue regeneration (Norte-01-0145-FEDER-000012), Projetos Estruturados de I& D& I - Norte-01-0145-FEDER-000012, Portugal 2020 - FEDER, and through EUROSPINE TRF (2017_05) by the project Disc degeneration-, immune-, and neuro-modulation. The authors also acknowledge FCT – Fundação para a Ciência e a Tecnologia, in the framework of the FCT Investigator Grant of RMG (IF/00638/2014), CC Junior Research contract (DL 57/2016/CP1360/CT0004) and the Ph.D. grant of JF (PD/BI/128357/2017). The authors would like to thank Serviço de Imunohemoterapia of Centro Hospitalar Universitário de São João (CHUSJ), for kindly donating Buffy Coats. |
| وصف الملف: | application/pdf |
| تدمد: | 1664-3224 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::3b9ad1bbccd2d526fadbdb46572c9c2f https://pubmed.ncbi.nlm.nih.gov/31333653 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....3b9ad1bbccd2d526fadbdb46572c9c2f |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 16643224 |
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