RESUMO
The U.S. government has sought to restrict immigration under the "America First" doctrine. These policies severely harm American science by stripping it of talent and eliminating a major driver of its innovation engine. We urge scientists to work to reverse these policies and forcefully condemn anti-immigrant sentiments.
Assuntos
Ciência , COVID-19/epidemiologia , COVID-19/virologia , Emigrantes e Imigrantes , Emigração e Imigração , Humanos , Pessoal de Laboratório , SARS-CoV-2/fisiologia , Estados UnidosAssuntos
Alergia e Imunologia , Pessoas Famosas , Virologia , Animais , História do Século XX , Humanos , CamundongosAssuntos
Distinções e Prêmios , Pesquisa Biomédica/história , Neoplasias da Mama/imunologia , Linfócitos T Reguladores/imunologia , Neoplasias da Mama/patologia , Feminino , História do Século XX , História do Século XXI , Humanos , Masculino , Retratos como Assunto , Linfócitos T Reguladores/patologiaAssuntos
Pesquisa Biomédica/história , Drosophila/fisiologia , Neurônios/fisiologia , Neurociências/história , Fisiologia/história , Animais , Distinções e Prêmios , História do Século XX , História do Século XXI , Humanos , Canais Iônicos/fisiologia , National Academy of Sciences, U.S. , Estados UnidosAssuntos
Linfócitos T CD4-Positivos/imunologia , Fator Regulador 1 de Interferon/fisiologia , Interferon gama/imunologia , Interleucina-12/fisiologia , Células Th1/imunologia , Animais , Linfócitos T CD4-Positivos/citologia , Diferenciação Celular , Fator Regulador 1 de Interferon/genética , Camundongos , Camundongos Knockout , Fator de Transcrição STAT4/fisiologia , Células Th1/citologiaRESUMO
Nearly half a century has passed since the first published description of interferons (IFNs). This commentary introduces the four accompanying review articles on type I IFN research and attempts to relate how the field of IFN research has been changing during its history.
Assuntos
Alergia e Imunologia/história , Interferons/história , Animais , História do Século XX , História do Século XXI , HumanosRESUMO
TNF-stimulated gene 6 (TSG-6) encodes a 35 kDa inducible secreted glycoprotein important in inflammation and female fertility. Previous studies have shown that TSG-6 has anti-inflammatory activity in models of acute and chronic inflammation. In the present study, we show that treatment of the RAW 264.7 murine macrophage cell line with TSG-6 protein up-regulates the expression of inducible cyclooxygenase-2 (COX-2), a key enzyme in inflammation and immune responses. This action of TSG-6 protein was abolished by heat denaturation, trypsin digestion, or anti-TSG-6 antibodies. TSG-6 treatment also resulted in a rapid increase in COX-2 mRNA levels, suggesting that TSG-6 up-regulates COX-2 gene expression. Up-regulation of COX-2 was accompanied by an increase in the production of prostaglandins, especially PGD2. As the PGD2 metabolite, 15-deoxy-Delta12,14-PGJ2, can act as a negative regulator of inflammation, these TSG-6 actions may explain, at least in part, the anti-inflammatory effect of TSG-6 observed in the intact organism.
Assuntos
Moléculas de Adesão Celular/farmacologia , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Macrófagos/enzimologia , Prostaglandina-Endoperóxido Sintases/metabolismo , Regulação para Cima , Animais , Linhagem Celular , Ciclo-Oxigenase 2 , Humanos , Macrófagos/metabolismo , Proteínas de Membrana , Camundongos , Prostaglandina-Endoperóxido Sintases/genética , Prostaglandinas/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Proteínas Recombinantes/farmacologia , Soro , Regulação para Cima/efeitos dos fármacosRESUMO
TSG-6 protein, up-regulated in inflammatory lesions and in the ovary during ovulation, shows anti-inflammatory activity and plays an essential role in female fertility. Studies in murine models of acute inflammation and experimental arthritis demonstrated that TSG-6 has a strong anti-inflammatory and chondroprotective effect. TSG-6 protein is composed of the N-terminal link module that binds hyaluronan and a C-terminal CUB domain, present in a variety of proteins. Interactions between the isolated link module and hyaluronan have been studied extensively, but little is known about the binding of full-length TSG-6 protein to hyaluronan and other glycosaminoglycans. We show that TSG-6 protein and hyaluronan, in a temperature-dependent fashion, form a stable complex that is resistant to dissociating agents. The formation of such stable complexes may underlie the activities of TSG-6 protein in inflammation and fertility, e.g. the TSG-6-dependent cross-linking of hyaluronan in the cumulus cell-oocyte complex during ovulation. Because adhesion to hyaluronan is involved in cell trafficking in inflammatory processes, we also studied the effect of TSG-6 on cell adhesion. TSG-6 binding to immobilized hyaluronan did not interfere with subsequent adhesion of lymphoid cells. In addition to immobilized hyaluronan, full-length TSG-6 also binds free hyaluronan and all chondroitin sulfate isoforms under physiological conditions. These interactions may contribute to the localization of TSG-6 in cartilage and to its chondroprotective and anti-inflammatory effects in models of arthritis.
