The Pro-inflammatory Effects of Glucocorticoids in the Brain

Autor(es)

Duque, Erica de Almeida ; Munhoz, Carolina Demarchi

• Tipo de documento: Artigo Científico
• Fonte: FRONTIERS IN ENDOCRINOLOGY; v. 7, JUN 28 2016.
• Citações Web of Science: 17

Resumo

Glucocorticoids are a class of steroid hormones derived from cholesterol. Their actions are mediated by the glucocorticoid and mineralocorticoid receptors, members of the superfamily of nuclear receptors, which, once bound to their ligands, act as transcription factors that can directly modulate gene expression. Through protein-protein interactions with other transcription factors, they can also regulate the activity of many genes in a composite or tethering way. Rapid non-genomic signaling was also demonstrated since glucocorticoids can act through membrane receptors and activate signal transduction pathways, such as protein kinases cascades, to modulate other transcriptions factors and activate or repress various target genes. By all these different mechanisms, glucocorticoids regulate numerous important functions in a large variety of cells, not only in the peripheral organs but also in the central nervous system during development and adulthood. In general, glucocorticoids are considered anti-inflammatory and protective agents due to their ability to inhibit gene expression of pro-inflammatory mediators and other possible damaging molecules. Nonetheless, recent studies have uncovered situations in which these hormones can act as pro-inflammatory agents depending on the dose, chronicity of exposure, and the structure/organ analyzed. In this review, we will provide an overview of the conditions under which these phenomena occur, a discussion that will serve as a basis for exploring the mechanistic foundation of glucocorticoids pro-inflammatory gene regulation in the brain. (AU)

• Processo FAPESP: 12/24727-4 - Avaliação dos efeitos terapêuticos da dexametasona (análogo sintético de glicocorticóides) e G1 (agonista do receptor de estrógeno acoplado a proteína G, GPER-1) na neuro-inflamação desencadeada por encefalomielite autoimune experimental
• Beneficiário: Carolina Demarchi Munhoz
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 10/13932-0 - Efeitos dos glicocorticóides na inflamação induzida por LPS em culturas primárias fronto-corticais de ratos neonatos
• Beneficiário: Erica de Almeida Duque
• Modalidade de apoio: Bolsas no Brasil - Mestrado
• Processo FAPESP: 08/55178-0 - Caracterização celular e das vias de sinalização do receptor de membrana GPR30 e sua participação nos efeitos neuroprotetores desencadeados pelo estrogeno no sistema nervoso central
• Beneficiário: Carolina Demarchi Munhoz
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores