RESUMO
Fibrotic diseases, such as idiopathic pulmonary fibrosis (IPF) and systemic scleroderma (SSc), are commonly associated with high morbidity and mortality, thereby representing a significant unmet medical need. Interleukin 11 (IL11)-mediated cell activation has been identified as a central mechanism for promoting fibrosis downstream of TGFß. IL11 signaling has recently been reported to promote fibroblast-to-myofibroblast transition, thus leading to various pro-fibrotic phenotypic changes. We confirmed increased mRNA expression of IL11 and IL11Rα in fibrotic diseases by OMICs approaches and in situ hybridization. However, the vital role of IL11 as a driver for fibrosis was not recapitulated. While induction of IL11 secretion was observed downstream of TGFß signaling in human lung fibroblasts and epithelial cells, the cellular responses induced by IL11 was quantitatively and qualitatively inferior to that of TGFß at the transcriptional and translational levels. IL11 blocking antibodies inhibited IL11Rα-proximal STAT3 activation but failed to block TGFß-induced profibrotic signals. In summary, our results challenge the concept of IL11 blockade as a strategy for providing transformative treatment for fibrosis.
Assuntos
Interleucina-11 , Fator de Crescimento Transformador beta , Humanos , Fator de Crescimento Transformador beta/metabolismo , Transdução de Sinais , Fibrose , Miofibroblastos/metabolismoRESUMO
O texto se refere ao período anterior ao surgimento das Instituições Psicanalíticas, em Recife. Os autores relembram, apoiados em suas memórias, o momento político, cultural e religioso dos anos 60 e 70, no Brasil, considerando sua importância na construção dos grupos que se interessam pela psicanálise e destacam a atuação de pessoas que, de algum modo colaboraram no movimento da psicanálise em Recife