ABSTRACT
Monocyte-derived macrophages contribute to pathogenesis in inflammatory diseases and their effector functions greatly depend on the prevailing extracellular milieu. Whereas M-CSF primes macrophages for acquisition of an anti-inflammatory profile, GM-CSF drives the generation of T cell-stimulatory and pro-inflammatory macrophages. Liver X Receptors (LXRα and LXRß) are nuclear receptors that control cholesterol metabolism and regulate differentiation of tissue-resident macrophages. Macrophages from rheumatoid arthritis and other inflammatory pathologies exhibit an enriched LXR pathway, and recent reports have shown that LXR activation raises pro-inflammatory effects and impairs the acquisition of the anti-Inflammatory profile of M-CSF-dependent monocyte-derived macrophages (M-MØ). We now report that LXR inhibition prompts the acquisition of an anti-inflammatory gene and functional profile of macrophages generated within a pathological environment (synovial fluid from Rheumatoid Arthritis patients) as well as during the GM-CSF-dependent differentiation of human monocyte-derived macrophages (GM-MØ). Mechanistically, inhibition of LXR results in macrophages with higher expression of the v-Maf Avian Musculoaponeurotic Fibrosarcoma Oncogene Homolog B (MAFB) transcription factor, which governs the macrophage anti-inflammatory profile, as well as over-expression of MAFB-regulated genes. Indeed, gene silencing experiments on human macrophages evidenced that MAFB is required for the LXR inhibitor to enhance the anti-inflammatory nature of human macrophages. As a whole, our results demonstrate that LXR inhibition prompts the acquisition of an anti-inflammatory transcriptional and functional profile of human macrophages in a MAFB-dependent manner, and propose the use of LXR antagonists as potential therapeutic alternatives in macrophage re-programming strategies during inflammatory responses.
Subject(s)
Arthritis, Rheumatoid , Granulocyte-Macrophage Colony-Stimulating Factor , Humans , Granulocyte-Macrophage Colony-Stimulating Factor/pharmacology , Macrophage Colony-Stimulating Factor/genetics , Up-Regulation , Macrophages/metabolism , Arthritis, Rheumatoid/pathology , Anti-Inflammatory Agents/metabolism , Liver X Receptors/genetics , Liver X Receptors/metabolism , MafB Transcription Factor/genetics , MafB Transcription Factor/metabolismSubject(s)
Brain Diseases, Metabolic/complications , Iron Overload/complications , Restless Legs Syndrome/complications , Brain/pathology , Brain Diseases, Metabolic/pathology , Humans , Iron Overload/pathology , Magnetic Resonance Imaging , Male , Middle Aged , Neuroimaging , Nocturnal Myoclonus Syndrome/complicationsABSTRACT
Se presenta el caso de una paciente de 39 años de edad con embarazo de 36 semanas de gestación e infarto agudo del miocardio atendida en el servicio de Ginecología y Obstetricia del Hospital ABC. El infarto agudo del miocardio durante el embarazo es poco frecuente y se ha calculado su frecuencia en aproximadamente 1/10,000 embarazos, se presenta con mayor frecuencia en el tercer trimestre, y debe tenerse presente ésta posibilidad para poder realizar su diagnóstico oportuno. La mortalidad se incrementa en forma significativa cuando éste se presenta en el tercer trimestre, cerca del inicio del trabajo de parto, durante el parto o en los primeros 7 días postparto. El manejo inicial de éstas pacientes debe realizarse en una unidad de cuidados intensivos y requiere de la participación de diversos especialistas, a fin de disminuir la mortalidad materna y fetal.
Subject(s)
Humans , Female , Pregnancy , Adult , Myocardial Infarction/physiopathology , Pregnancy Complications, Cardiovascular/therapy , Pregnancy Trimester, ThirdABSTRACT
Se presenta el caso de una mujer de 31 años, con embarazo de termino asociado a cardiomiopatía hipertrófica primaria que fue atendida en el Servicio de Gineco-Obstetricia en el Hospital ABC. el embarazo, trabajo de parto y parto evolucionaron sin complicaciónes obstétricas y/o perinatales. Se comenta la etiología, clasificación diagnóstico y tratamiento de ésta cardiopatía que ha sido reportada durante el embarazo en pocas publicaciones.
