ABSTRACT
BACKGROUND AND OBJECTIVES: Cyclooxygenase-2 (COX-2) is a key molecule in the biosynthesis of prostaglandins, which are important inflammatory mediators in human airway inflammatory diseases. This study was designed to investigate the effects of several COX inhibitors on the interleukin-1beta (IL-1beta)-mediated COX-2 expression in human airway epithelial cells. MATERIALS AND METHOD: We observed the effects of anti-inflammatory drugs such as budesonide, triamcinolone, dexamethasone, NS-398, indomethacin, salicylate and resveratrol on the IL-1beta-induced COX-2 expression in cultured human airway NCI-H292 epithelial cells. The levels of COX-2 mRNA and COX-2 protein were analyzed by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot. RESULTS: NS398, reveratrol and three corticosteroids strongly suppressed the IL-1beta-mediated COX-2 expression. However, indomethacin and salicylate did not inhibit or inhibited only weakly. CONCLUSION: The extent of IL-1beta-induced supression of COX-2 expression in the cultured human airway NCI-H292 epithelial cells depended on the kinds of anti-inflammatory drugs.
Subject(s)
Humans , Adrenal Cortex Hormones , Blotting, Western , Budesonide , Cyclooxygenase 2 , Dexamethasone , Epithelial Cells , Indomethacin , Interleukin-1 , Interleukin-1beta , Prostaglandin-Endoperoxide Synthases , Prostaglandins , RNA, Messenger , TriamcinoloneABSTRACT
Sinonasal Undifferentiated Carcinoma (SNUC) is a very rare, highly aggressive malignant tumor of the nasal cavity and paranasal sinuses. SNUC tends to present with advanced-stage disease, often with intracranial invasion. It requires an aggressive multimodality therapy that includes surgical resection. A cure rate of less than 20% is generally reported in the literature, with most patients dying within 1 year of onset of the disease. Three patients diagnosed as SNUC were treated at the Yeungnam University Medical Center between the years 2000 and 2003 were analyzed retrospectively. All patients presented with the disease very advanced. The three cases were given chemotherapy or chemotherapy with radiotherapy. Two patients died of the disease, surviving only 6 and 11 months following treatment, respectively. We did a follow-up on just the one remaining case with incomplete controlled disease for 27 months. The overall prognosis of SNUC is very poor. We consider that more intensive multimodality therapies are recommended for all patients with SNUC.
Subject(s)
Humans , Academic Medical Centers , Carcinoma , Drug Therapy , Follow-Up Studies , Nasal Cavity , Paranasal Sinuses , Prognosis , Radiotherapy , Retrospective StudiesABSTRACT
BACKGROUND AND OBJECTIVES: Vasointestinal peptide (VIP) is an important neurotransmitter involved in the regulation of mucus secretion, but the relationship of VIP and mucin genes is not clear. This study was designed to investigate the effect of VIP on MUC2/5AC genes expression and mucin secretion in human airway epithelial cells. MATERIALS AND METHOD: The mRNA levels of MUC2/5AC genes and mucin secretion were determined by RT-PCR and the immunoblot method in cultured human airway NCI-H292 epithelial cells. RESULTS: VIP (10-6-10-10 M) induced MUC2/5AC gene expression and mucin secretion in a reverse dose-dependant manner. The maximum expression of mRNA and mucin secretion level of MUC2/5AC was 10-10 M of VIP. Actinomycin D inhibited the VIP-mediated MUC2/5AC gene expression and mucin secretion, but cycloheximide did not. Budesonide attenuated the VIP-mediated MUC2/5AC genes expression and mucin secretion. RU-486, a glucocorticoid receptor antagonist, restored the inhibitory effect of budesonide. CONCLUSION: These results suggest that VIP regulates MUC2/5AC gene expression and secret mucin by transcriptional regulation, and that budesonide inhibits the VIP-mediated MUC2/5AC genes expression and mucin secretion through the glucocorticoid receptor.
Subject(s)
Humans , Budesonide , Cycloheximide , Dactinomycin , Epithelial Cells , Gene Expression , Mifepristone , Mucins , Mucus , Neurotransmitter Agents , Receptors, Glucocorticoid , RNA, Messenger , Vasoactive Intestinal PeptideABSTRACT
BACKGROUND AND OBJECTIVES: Mucus hypersecretion is a hallmark of many respiratory inflammatory diseases such as asthma, bronchitis and sinusitis. While the current therapeutic pharmacological approaches to reducing mucus hypersecretion are limited, clinical studies have suggested that glucocorticoids reduce mucus secretion in patients with airway disease. However, the effect of glucocorticoids on mucus hypersecretion is not clear. Recently, we observed that IL-1beta induces MUC2 gene expression and mucin secretion in a previous experiment. This study was designed to investigate the effects of budesonide on the IL-1beta-mediated MUC2/5AC genes expression and mucin secretion. MATERIALS AND METHOD: We observed the steady state mRNA level of MUC2/5AC genes using RT-PCR and mucin protein using immunoassay method in cultured human airway NCI-H292 epithelial cells. RESULTS: Budesonide attenuated IL-1beta-mediated MUC2/5AC gene expression as well as mucin secretion. The attenuated effect of budesonide was in a dose-dependent pattern. This attenuated effect of budesonide was blocked by glucocorticoid receptor antagonist, RU-486. CONCLUSION: This result suggests that budesonide suppresses the IL-1beta-mediated MUC2/5AC genes expression and mucin secretion via blockage of glucocorticoid receptor.