Inhibition of Macrophage Nuclear Factor-κB Leads to a Dominant Anti-Inflammatory Phenotype that Attenuates Glomerular Inflammation in Vivo
| Autor: | Heather M. Wilson, Salah Chettibi, Christian Jobin, David C. Kluth, Andrew J. Rees, David Walbaum |
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| Rok vydání: | 2005 |
| Předmět: |
Kidney Glomerulus
Macrophage-activating factor Bone Marrow Cells Electrophoretic Mobility Shift Assay Inflammation In Vitro Techniques Biology Pathology and Forensic Medicine Nitric oxide chemistry.chemical_compound Transduction Genetic In vivo medicine Animals Macrophage inflammatory protein Nephritis Macrophages NF-kappa B Macrophage Activation Flow Cytometry medicine.disease Interleukin-10 Rats Original Research Paper Interleukin 10 Phenotype chemistry Immunology Cancer research Tumor necrosis factor alpha medicine.symptom |
| Zdroj: | The American Journal of Pathology. 167:27-37 |
| ISSN: | 0002-9440 |
| DOI: | 10.1016/s0002-9440(10)62950-1 |
| Popis: | Infiltrating macrophages (mphi) can cause injury or facilitate repair, depending on how they are activated by the microenvironment. Studies in vitro have defined the roles of individual cytokines and signaling pathways in activation, but little is known about how macrophages integrate the multiple signals they receive in vivo. We inhibited nuclear factor-kappaB in bone marrow-derived macrophages (BMDMs) by using a recombinant adenovirus expressing dominant-negative IkappaB (Ad-IkappaB). This re-orientated macrophage activation so they became profoundly anti-inflammatory in settings where they would normally be classically activated. In vitro, the lipopolysaccharide-induced nitric oxide, interleukin-12, and tumor necrosis factor-alpha synthesis was abrogated while interleukin-10 synthesis increased. In vivo, fluorescently labeled BMDMs transduced with Ad-IkappaB and injected into the renal artery significantly reduced inducible nitric oxide synthase and MHC class II expression when activated naturally in glomeruli of rats with nephrotoxic nephritis. Furthermore, although they only comprised 15% of glomerular macrophages, their presence significantly reduced glomerular infiltration and activation of host macrophages. Injury in nephrotoxic nephritis was also decreased when assessed morphologically and by severity of albuminuria. The results demonstrate the power of Ad-IkappaB-transduced BMDMs to inhibit injury when activated by acute immune-mediated inflammation within the glomerulus. |
| Databáze: | OpenAIRE |
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