ABSTRACT
Objective To explore the possible upstream signal transduction mechanisms responsible for the decrease of glucocorticoid receptor (GR)α/GRβ in chronic rhinosinusitis (CRS) in vitro. Methods The GRα/GRβ decrease cell model was established by IL-1β-induced human nasal epithelia (HNE) in vitro. Changes in the protein and mRNA expression of GRα, GRβ and the key enzymes in the p38MAPK and NF-κB pathways were measured respectively, before and after being induced with different doses of IL-1β and specific inhibitors of p38MAPK and NF-κB. Analysis of variance (ANOVA) was used to analyze the data. Results With IL-1β-induction, the GRα/GRβ ratio declined in both a time-dependent manner and a concentration-dependent manner in HNE, which demonstrated the successful establishment of a GRα/GRβ decrease model in vitro. After cultured HNE were induced with the same set of IL-1β, the p38MAPK and NF-κB signal pathways were also activated. Either a specific inhibitor (SB203580) of the p38MAPK pathway or a specific inhibitor (PDTC) of the NF-κB pathway increased the GRα/GRβ ratio at the meantime of inhibiting their pathways. The expressions of phospho-NF-κBp50 and phospho-NF-κBp65 were significantly decreased by SB203580. PDTC had no influence on the expression of the key enzymes in the p38MAPK. Conclusion The decrease of GRα/GRβ ratio in HNE induced by IL-1β in vitro is induced through the p38MAPK/NF-κB signal pathways.
ABSTRACT
Background and purpose:The development of nasopharyngeal carcinoma in rat and transformation of embryo nasophryngeal epithelia induced by N,N'-dinitrosopiperazine (DNP) were interfered by Yiqijiedu formular medicine via inhibiting telomerase. We investigated the impact of Yiqijiedu formula on precancerous lesion of nasal and nasopharyngeal epithelia in TgN (p53mt-LMP1) / HT mice induced by DNP and on its expression level of c-jun and p16 genes. Methods:The fourth generation TgN (p53mt-LMP1) / HT mice aged 5 months were randomly divided into 2 groups:(1)TgN(p53mt-LMP1)/HT cancerous lesion-inducing group (group A) was treated by normal saline with 15ml/kg, and Chinese traditional medicine treating group (group B) was treated by Yiqijiedu formular drug with 12.91 g/(kg?d). C57BL/6J wild-type mice were chosen as negative control group (group C) treated by normal saline with 15ml/kg. Epithelial tissue samples were taken from nasal cavity and nasopharyngnx of mice respectively for pathohistological evaluation by H-E staining procedures, and expression level of c-Jun and p16 in these tissue sampleswere determined by immunohistochemical methods and western blot. Results:The occurrence rates of precancerous lesions in nasal and/or nasopharyngeal epithelia in Group C, A and B were 0, 90% and 10% respectively (P