RESUMEN
It is known that herpes simplex virus type 2 (HSV-2) triggers the activation of Toll-like receptor (TLR) 9 signaling pathway and the consequent production of antiviral cytokines in dendritic cells. However, the impact of HSV-2 infection on TLR9 expression and signaling in genital epithelial cells, the primary HSV-2 targets, has yet to be determined. In the current study, by using both human genital epithelial cell lines and primary genital epithelial cells as models, we found that HSV-2 infection enhances TLR9 expression at both mRNA and protein levels. Such enhancement is virus replication-dependent and CpG-independent, while the HSV-2-mediated upregulation of TLR9 does not activate TLR9 signaling pathway. Mechanistically, a SP1 binding site on TLR9 promoter appears to be essential for HSV-2-induced TLR9 transactivation. Upon HSV-2 infection, SP1 translocates from the cytoplasm to the nucleus, and consequently binds to TLR9 promoter. By using specific inhibitors, the JNK signaling pathway is shown to be involved in the HSV-2-induced TLR9 transactivation, while HSV-2 infection increases the phosphorylation but not the total level of JNK. In agreement, antagonism of JNK signaling pathway inhibits the HSV-2-induced SP1 nuclear translocation. Taken together, our study demonstrates that HSV-2 infection of human genital epithelial cells promotes TLR9 expression through SP1/JNK signaling pathway. Findings in this study provide insights into HSV-2-host interactions and potential targets for immune intervention.
Asunto(s)
Genitales/virología , Herpesvirus Humano 2/fisiología , Proteínas Quinasas JNK Activadas por Mitógenos/fisiología , Factor de Transcripción Sp1/fisiología , Receptor Toll-Like 9/genética , Células Epiteliales/virología , Femenino , Células HeLa , Humanos , Sistema de Señalización de MAP Quinasas/fisiología , Masculino , Regiones Promotoras Genéticas , Transducción de Señal/fisiología , Receptor Toll-Like 9/fisiología , Regulación hacia Arriba , Replicación ViralRESUMEN
PURPOSE: The purpose of this study was to determine the significance and frequency of rapid gastric emptying (RGE) in clinical practice and to examine its relationship to age, gender, and presenting symptoms. METHODS: The review included 750 patients who underwent scintigraphic gastric emptying studies (GES) within the past 11 years. In 80 patients with RGE, the mean gastric emptying time (GET) in female and male patients was compared with study gender differences. Similarly, the mean GET in young and old patients was compared with study age differences. The presenting symptoms and conditions indicating GES were noted. RESULTS: RGE was found in 80 of 750 study patients (10.7%). RGE was equally common in both sexes. Younger patients (mean age, 34.3 +/- 9.5 years) and older patients (mean age, 67.3 +/- 11.6 years) had similar mean GETs. Most patients with RGE presented with symptoms that mimicked gastroparesis. CONCLUSIONS: RGE has no relationship to age or gender. RGE may be representative of early dumping syndrome in most patients. GES help make a clear distinction between early dumping syndrome and gastroparesis, which can present with similar symptoms.