RESUMEN
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.
Asunto(s)
Quinasas MAP Reguladas por Señal Extracelular/antagonistas & inhibidores , Terapia de Inmunosupresión , Activación de Linfocitos/efectos de la radiación , FN-kappa B/antagonistas & inhibidores , Receptores de Antígenos de Linfocitos T/antagonistas & inhibidores , Transducción de Señal/efectos de la radiación , Linfocitos T/efectos de la radiación , Rayos Ultravioleta , Citocinas/antagonistas & inhibidores , Citocinas/biosíntesis , Citocinas/efectos de la radiación , Relación Dosis-Respuesta en la Radiación , Activación Enzimática/efectos de la radiación , Quinasas MAP Reguladas por Señal Extracelular/fisiología , Quinasas MAP Reguladas por Señal Extracelular/efectos de la radiación , Humanos , Proteínas Quinasas JNK Activadas por Mitógenos/metabolismo , Proteínas Quinasas JNK Activadas por Mitógenos/efectos de la radiación , Células Jurkat , Activación de Linfocitos/inmunología , FN-kappa B/biosíntesis , FN-kappa B/fisiología , FN-kappa B/efectos de la radiación , Proteínas Proto-Oncogénicas c-jun/antagonistas & inhibidores , Proteínas Proto-Oncogénicas c-jun/biosíntesis , Proteínas Proto-Oncogénicas c-jun/efectos de la radiación , Receptores de Antígenos de Linfocitos T/fisiología , Receptores de Antígenos de Linfocitos T/efectos de la radiación , Transducción de Señal/inmunología , Linfocitos T/enzimología , Linfocitos T/metabolismo , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo , Proteínas Quinasas p38 Activadas por Mitógenos/efectos de la radiaciónRESUMEN
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.
