Hyperosmolar solutions stimulate mucus secretion in the ferret trachea.

STUDY OBJECTIVES: Inhalation of hypertonic saline or mannitol solutions acutely increases mucociliary clearance. Because increased clearance is often coupled with increased mucus secretion, we hypothesized that hyperosmolar agents would stimulate mucus secretion. SETTING AND SUBJECTS: The isolated tracheae of healthy young adult ferrets were studied in a basic research laboratory. MEASUREMENTS AND RESULTS: We demonstrated that there was a dose-dependent increase in mucin secretion by enzyme-linked lectin assay after incubation with 1.69 g/dL (597 mOsm/L), 3.69 g/dL (1,192 mOsm/L), 5.69 g/dL (1,823 mOsm/L), and 10.69 g/dL (3,612 mOsm/L) of saline solution over Krebs-Henseleit solution control (288 mOsm/L) [p < 0.01 for 1.69 g/dL of saline solution and p < 0.0001 for others]. Mannitol solution, 15 g/dL (1,040 mOsm/L), also significantly increased mucin secretion (n = 4, p < 0.005). There was a 47% and 54% increase in secretion of the serous cell product lysozyme after exposure to 3.69 g/dL (1,192 mOsm/L) and 10.69 g/dL (3,612 mOsm/L) saline solutions, respectively (n = 5, p < 0.05). Secretion was only stimulated when the hyperosmolar exposure was on the luminal side of the epithelium. Mucin secretion was induced within minutes of 3.69 g/dL of saline solution exposure, and this increased mucin secretion quickly peaked. The ratio of mucin to lysozyme secretion was approximately 2. This ratio appeared to be independent of the osmotic concentration of the stimulus and therefore of secretory rate. CONCLUSIONS: Mucus secretion is markedly stimulated in response to hyperosmolarity. This may be a protective response. These results also suggest that the therapeutic use of hyperosmolar aerosols should be evaluated with care when used for patients with mucus hypersecretion and impaired mucus clearance.

Effects of dexamethasone on mucin gene expression in cultured human nasal epithelial cells.

OBJECTIVE: To clarify 1) which mucin gene expression is influenced by glucocorticoid and 2) whether glucocorticoid influences steady-state mucin expression or mucin gene expression induced by lipopolysaccharide. METHODS: Dissociated cells obtained from nasal polyps were cultured on a collagen gel substrate in an air-liquid interface. Dexamethasone was added to the culture medium in the steady-state and prior to the stimulation by LPS. RNAs were extracted from culture cells, and semiquantitative reverse transcriptase-polymerase chain reaction was performed for MUC2, MUC5AC, MUC5B, MUC8, and beta-actin. RESULTS: Dexamethasone did not influence steady-state messenger RNA levels of either mucin gene. Dexamethasone suppressed lipopolysaccharide-induced messenger RNA levels of MUC8. CONCLUSION: Glucocorticoid does not influence steady-state mucin gene expression but suppresses mucin gene expression induced by secretagogues such as lipopolysaccharide.

Mucin gene expression in the effusions of otitis media with effusion.

OBJECTIVES: The purpose of the study is to know if mucin gene expression can be detected in the middle ear effusion and if so, which mucin genes are expressed in the effusions. METHODS: Mucin gene expression in the middle ear effusions obtained from five patients with otitis media with effusion were analyzed by reverse transcription-polymerase chain reaction. Ribonucleic acids (RNAs) were extracted from the effusion and the expression of 12 mucin genes was analyzed by reverse transcription-polymerase chain reaction. RESULTS: Mucin gene expression examined by reverse transcription-polymerase chain reaction indicated the expression of MUC1, MUC4, MUC5AC, MUC6, MUC7, MUC8, MUC9, MUC11 and MUC12 mRNA in the effusion. This mucin gene expression was similar to that in BEAS-2B cell, a bronchial epithelial cell line. CONCLUSION: Middle ear effusion can give us valuable information on mucin gene expression in the middle ear. There is similarity between mucin gene expression in the middle ear effusion and that in the bronchial epithelia.

Physical and transport properties of sputum from children with idiopathic bronchiectasis.

BACKGROUND: Childhood idiopathic bronchiectasis (IB) unrelated to cystic fibrosis (CF) or known immunodeficiency remains a common problem among indigenous populations in developed and developing countries. The physical and transport properties of sputum among children with IB have not been described, and these properties may suggest therapies that would be particularly effective for this group of children. METHODS: Sputum from children in stable condition with IB and chronic daily productive cough was collected to measure viscosity, elasticity, cohesivity, adhesivity, and mucociliary and cough transportability in vitro. The results were compared to banked data from the sputa of children with CF and adults with chronic bronchitis (CB) measured by the same methods. RESULTS: Sputa from children with CF and adults with CB had similar values for viscosity, elasticity, frictional adhesion, cough transportability, and mucociliary transportability. The elasticity of sputum from children with IB was 12 to 20%, respectively, of the value of CB and CF sputum (p < 0.01). The viscosity of sputum from children with IB was 23 to 32%, respectively, of the value of CB and CF sputum (p < 0.02). The surface frictional adhesion for sputum from children with IB was 55% of the values from both CF and CB sputa (p < 0.0001). Cough transportability for sputum from children with IB was 43 to 54% greater, respectively, than that for sputum from CB and CF patients (p < 0.0001). Mucociliary transportability was similar for all three groups (p > 0.05). CONCLUSIONS: The physical and transport properties of sputum from children with IB who are stable in the outpatient setting are substantially different and lead to improved cough transportability compared to sputum from children with CF or adults with CB. Therapies that focus on cough may be sufficient to improve airway mucus clearance in children with IB. Sputum properties may explain in part the different clinical course of children with IB compared to children with CF.

Pranlukast inhibits NF-kappaB activation and MUC2 gene expression in cultured human epithelial cells.

Pranlukast is a selective cysteinyl leukotriene(1 )(cysLT(1)) receptor antagonist, and is now widely used in the treatment of asthma. The anti-asthmatic effect of pranlukast may be rendered not only by antileukotriene activity, but also by other pharmacological activity. This study was designed to investigate whether pranlukast had inhibitory effects on nuclear factor-kappaB (NF-kappaB) activation and mucin gene expression in cultured human epithelial cells. Luciferase assay was mainly used for analysis. Cultured epithelial cells were transfected with NF-kappaB luciferase vector, MUC2 or MUC5AC luciferase vectors. Lipopolysaccharide (LPS) significantly increased NF-kappaB activation in NCI-H292 cells, which was inhibited by the pretreatment by pranlukast in a dose-dependent manner. Either LTD(4) or pranlukast alone did not increase NF-kappaB activation in NCI-H292 cells. Pranlukast also inhibited NF-kappaB activation induced by phorbol 12-myristate 13-acetate (PMA). Pranlukast also significantly inhibited LPS-induced MUC2 mRNA expression by reverse transcription-polymerase chain reaction (RT-PCR) analysis in NCI-H292 cells. Pranlukast also inhibited LPS-induced MUC2 gene expression in HM3-MUC2 cells. However, pranlukast did not inhibit MUC5AC gene transcription activity induced by lipoteichoic acid (LTA) in NCI-H292 cells. These results suggest that pranlukast may inhibit NF-kappaB activation and MUC2 gene transcription through pathways distinct from cysLT(1) receptor antagonism in cultured human epithelial cells.

Lipoblastoma of the neck: a case report and literature review.

Lipoblastoma is a rare benign tumor arising from embryonic white fat. We describe a case of huge lipoblastoma of the neck in a 1-year-old boy. Magnetic resonance imaging (MRI) revealed a 7 x 7 cm neck mass that extruded into the parapharyngeal and paratracheal spaces. At the operation, a well-circumscribed and extensively growing tumor was completely removed. Histopathologic examination showed that the tumor contained lobulated mature adipose tissue and myxoid tissue with lipoblasts and other immature fat cells. The postoperative course was uneventful, and no recurrence of tumor has been noted in more than 2 years follow-up.

Roxithromycin suppresses mucin gene expression in epithelial cells.

Macrolide antibiotics are believed to inhibit mucus secretion but the mechanism of action is unclear. This study was designed to investigate an effect of roxithromycin on MUC2 gene expression in cultured intestinal epithelial cells (HM3-MUC2 cells). A reporter gene assay was used for analysis. Roxithromycin suppressed MUC2 gene transcriptional activity in a dose-dependent manner in HM3-MUC2 cells. Phorbol 12-myristate 13-acetate (PMA), lipoteichoic acid (LTA), lipopolysaccharide (LPS) and leukotriene D4 (LTD4) significantly increased MUC2 luciferase activities in the following order: PMA > LTA > LTD4 > LPS. Roxithromycin also decreased MUC2 gene transcriptional activity induced by PMA in a dose-dependent manner. NF-kappaB activation, but not AP-1 activation, was significantly suppressed by roxithromycin in HM3-MUC2 cells. A suppression of NF-kappaB activation was also observed in NCI-H292 cells. These results suggest that roxithromycin suppresses MUC2 gene expression in epithelial cells and that this suppression is probably via inhibition of NF-kappaB activation.