RESUMO
UV irradiation is carcinogenic and immunosuppressive. Previous studies indicate that UV-mediated alteration of APCs and induction of suppressor T cells play a critical role in UV-induced immune suppression. In this study, we show that UV irradiation can directly (independently of APCs and suppressor T cells) inhibit T cell activation by blocking TCR-mediated phosphorylation of ERK and IkappaB via overactivation of the p38 and JNK pathways. These events lead to the down-modulation of c-Jun, c-Fos, Egr-1, and NF-kappaB transcription factors and thereby inhibit production of cytokines, e.g., IL-2, IL-4, IFN-gamma, and TNF-alpha, upon TCR stimulation. We also show that UV irradiation can suppress preactivated T cells, indicating that UV irradiation does not only impair T cell function in response to T cell activation, but can also have systemic effects that influence ongoing immune responses. Thus, our data provide an additional mechanism by which UV irradiation directly suppresses immune responses.
Assuntos
MAP Quinases Reguladas por Sinal Extracelular/antagonistas & inibidores , Terapia de Imunossupressão , Ativação Linfocitária/efeitos da radiação , NF-kappa B/antagonistas & inibidores , Receptores de Antígenos de Linfócitos T/antagonistas & inibidores , Transdução de Sinais/efeitos da radiação , Linfócitos T/efeitos da radiação , Raios Ultravioleta , Citocinas/antagonistas & inibidores , Citocinas/biossíntese , Citocinas/efeitos da radiação , Relação Dose-Resposta à Radiação , Ativação Enzimática/efeitos da radiação , MAP Quinases Reguladas por Sinal Extracelular/fisiologia , MAP Quinases Reguladas por Sinal Extracelular/efeitos da radiação , Humanos , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Proteínas Quinases JNK Ativadas por Mitógeno/efeitos da radiação , Células Jurkat , Ativação Linfocitária/imunologia , NF-kappa B/biossíntese , NF-kappa B/fisiologia , NF-kappa B/efeitos da radiação , Proteínas Proto-Oncogênicas c-jun/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-jun/biossíntese , Proteínas Proto-Oncogênicas c-jun/efeitos da radiação , Receptores de Antígenos de Linfócitos T/fisiologia , Receptores de Antígenos de Linfócitos T/efeitos da radiação , Transdução de Sinais/imunologia , Linfócitos T/enzimologia , Linfócitos T/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/efeitos da radiaçãoRESUMO
Relaxin in human pregnancy is both a systemic hormone from the corpus luteum and an autocrine/paracrine hormone at the maternal-fetal interface formed by the decidua/placenta and fetal membranes. We have focused our studies on the autocrine/paracrine roles of relaxin, especially in the preterm premature rupture of the fetal membranes, which causes 30-40% of preterm births. By using different techniques and different tissue collections, our laboratory has shown that expression of the relaxin genes and proteins in the decidua and placenta is increased in patients with preterm premature rupture of the fetal membranes. Relaxin binding and the expression of LGR7 are primarily in the chorion and decidua and are downregulated after spontaneous labor and delivery both at term and preterm. However, expression of LGR7 in the fetal membranes is significantly greater in all clinical situations at preterm than term, suggesting an important role for relaxin in these tissues at that time. The roles of the relaxin system in three potential causes of preterm birth are discussed: in the growth and proliferation of the membranes important for fetal membrane accommodation to fetal and placental growth, in acute infection, and in the inflammatory response leading to the initiation of labor.