ABSTRACT
In the current literature, there is evidence that psychological factors can affect the incidence and progression of some cancers. Interleukin 6 (IL-6) is known to be elevated in individuals experiencing chronic stress and is also involved in oncogenesis and cancer progression. However, the precise mechanism of IL-6 induction by the stress-related hormone norepinephrine (NE) is not clear, and, furthermore, there are no reports about the effect of NE on IL-6 expression in gastric epithelial cells. In this study, we examined the effect of NE on IL-6 expression in immortalized human gastric epithelial cells (GES-1 cells). Using real-time PCR and enzyme-linked immunoassay, we demonstrated that NE can induce IL-6 mRNA and protein expression in GES-1 cells. The induction is through the β-adrenergic receptor-cAMP-protein kinase A pathway and mainly at the transcriptional level. Progressive 5′-deletions and site-directed mutagenesis of the parental construct show that, although activating-protein-1 (AP-1), cAMP-responsive element binding protein (CREB), CCAAT-enhancer binding protein-β (C/EBP-β), and nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) binding sites are all required in the basal transcription of IL-6, only AP-1 and CREB binding sites in the IL-6 promoter are required in NE-induced IL-6 expression. The results suggest that chronic stress may increase IL-6 secretion of human gastric epithelial cells, at least in part, by the stress-associated hormone norepinephrine, and provides basic data on stress and gastric cancer progression.
Subject(s)
Humans , Epithelial Cells/drug effects , /metabolism , Norepinephrine/pharmacology , Signal Transduction/physiology , Cell Line , Enzyme-Linked Immunosorbent Assay , Epithelial Cells/metabolism , Gastric Mucosa/drug effects , Gastric Mucosa/metabolism , Gene Expression Regulation/physiology , /genetics , NF-kappa B/metabolism , Norepinephrine/metabolism , Real-Time Polymerase Chain Reaction , RNA, Messenger/metabolism , Receptors, Adrenergic, beta/metabolism , Transcription Factors/physiology , Up-RegulationABSTRACT
OBJECTIVE: To evaluate the changes of plasma levels of N-terminal probrain natriuretic pepide (NT-proBNP) and microalbuminuria (MAU) in patients with heart failure and the correlation between them. METHODS: Ninety-one patients with heart failure were divided into different groups according to different stages of heart failure. Plasma levels of NT-proBNP were measured by microsome enzyme immuno-assay (MEIA). Plasma levels of MAU were determined by immune scattering turbidimetry (ICTM). Simultaneously, left ventricular ejection fraction (LVEF) and left ventricular end diastolic diameter (LVEDD) were measured by Doppler echocardiography for all patients. The correlation of NT-proBNP and MAU was evaluated at different stages of heart failure. RESULTS: The plasma levels of NT-proBNP and MAU increased with the severity of heart failure. There was a high correlation between NT-proBNP and MAU (r = 0.885, p < 0.001). CONCLUSION: Both NT-proBNP and MAU levels were closely associated with the severity of heart failure.
OBJETIVO: Evaluar los cambios en los niveles de plasma de la fracción N-terminal del propéptido natriurético cerebral (NT-proBNP), y la microalbuminuria (MAU) en pacientes con insuficiencia cardíaca y la correlación entre ambas. MÉTODOS: Noventa y un pacientes con insuficiencia cardíaca fueron divididos en diferentes grupos de acuerdo con las diferentes etapas de insuficiencia cardíaca. Los niveles de plasma de NT-proBNP fueron medidos mediante inmunoensayo enzimático microsomal (MEIA). Los niveles plasmáticos de MAU se determinaron mediante turbidimetría inmune de difusión (ICTM). Simultáneamente, a todos los pacientes se les midió la fracción de eyección ventricular izquierda (FEVI) y el diámetro de fin de diástole del ventrículo izquierdo (DFDVI), mediante ecocardiografía Doppler. La correlación de NT-proBNP y MAU fue evaluada en diferentes etapas de la insuficiencia cardíaca. RESULTADOS: Los niveles de plasma de NT-proBNP y MAU aumentaron con la severidad de la insuficiencia cardíaca. Hubo una alta correlación entre NT-proBNP y MAU (r = 0.885, p < 0.001). CONCLUSIÓN: Tanto los niveles de NT-proBNP como los de MAU estuvieron estrechamente asociados con la severidad de la insuficiencia cardíaca.