RESUMO
Returning astronauts have experienced altered immune function and increased vulnerability to infection during spaceflights dating back to Apollo and Skylab. Lack of immune response in microgravity occurs at the cellular level. We analyzed differential gene expression to find gravity-dependent genes and pathways. We found inhibited induction of 91 genes in the simulated freefall environment of the random positioning machine. Altered induction of 10 genes regulated by key signaling pathways was verified using real-time RT-PCR. We discovered that impaired induction of early genes regulated primarily by transcription factors NF-kappaB, CREB, ELK, AP-1, and STAT after crosslinking the T-cell receptor contributes to T-cell dysfunction in altered gravity environments. We have previously shown that PKA and PKC are key early regulators in T-cell activation. Since the majority of the genes were regulated by NF-kappaB, CREB, and AP-1, we studied the pathways that regulated these transcription factors. We found that the PKA pathway was down-regulated in vg. In contrast, PI3-K, PKC, and its upstream regulator pLAT were not significantly down-regulated by vectorless gravity. Since NF-kappaB, AP-1, and CREB are all regulated by PKA and are transcription factors predicted by microarray analysis to be involved in the altered gene expression in vectorless gravity, the data suggest that PKA is a key player in the loss of T-cell activation in altered gravity.
Assuntos
Regulação para Baixo , Perfilação da Expressão Gênica , Linfócitos T/citologia , Astronautas , Análise por Conglomerados , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/biossíntese , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Regulação da Expressão Gênica , Gravitação , Humanos , Sistema Imunitário , Ativação Linfocitária , Modelos Biológicos , Modelos Estatísticos , NF-kappa B/biossíntese , Análise de Sequência com Séries de Oligonucleotídeos , Proteína Quinase C/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fatores de Transcrição STAT/biossíntese , Transdução de Sinais , Linfócitos T/metabolismo , Fator de Transcrição AP-1/biossíntese , Proteínas Elk-1 do Domínio ets/biossínteseRESUMO
Up to now, the inversion trauma of the ankle joint is one of the most important and frequent injuries. The functional treatment has come to a point of advantages in the therapeutic regime. Nevertheless a follow-up is necessary. In a follow-up examination, in the average of 27 months after trauma, 90.3% of the patients have satisfactory or better results. In all patients a stress tenography is carried out. Between radiologic finding and clinical situation is no direct correlation. In the treatment of fibular ligament rupture it is necessary to find out the patients with chronic instability. They have a benefit in an early reconstructive operation of the fibular ligaments.
