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Background Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) release extracellular vesicles (EVs). E. coli–derived and S. aureus–derived EVs are associated with neutrophilic respiratory inflammation. In neutrophilic respiratory inflammation of human, expression of mucin is increased in airway epithelial cells and is associated with increased morbidity and mortality of the affected patients. However, no study on the effects of EVs on expression of mucin genes has been reported in airway epithelial cells. Therefore, this study was conducted in order to examine the effects and the brief signaling pathways of E. coli–derived and S. aureus–derived EVs on MUC5AC expression in human airway epithelial cells. Methods In mucin-producing human NCI-H292 airway epithelial cells and primary cultures of normal nasal epithelial cells, the effects and signaling pathways of E. coli–derived and S. aureus–derived EVs on MUC5AC expression were examined using reverse transcription–polymerase chain reaction (RT-PCR), real-time PCR, enzyme immunoassay, and immunoblot analysis with several specific inhibitors and small interfering RNA (siRNA). Results E. coli–derived and S. aureus–derived EVs induced MUC5AC expression. E. coli–derived and S. aureus–derived EVs significantly activated phosphorylation of extracellular signal related kinase 1/2 (ERK1/2) mitogen-activated protein kinase (MAPK) and p38 MAPK. ERK1/2 MAPK inhibitor, p38 MAPK inhibitor, ERK1/2 MAPK siRNA, and p38 MAPK siRNA significantly blocked E. coli–derived and S. aureus–derived EVs induced MUC5AC messenger RNA (mRNA) expression. Conclusion The results of this study suggest that E. coli–derived and S. aureus–derived EVs induced MUC5AC expression via ERK1/2 and p38 MAPK signaling pathways in human airway epithelial cells.

Background Inhalation of cadmium can lead to development of inflammatory airway diseases such as acute pulmonary edema and chronic obstructive pulmonary disease. In inflammatory airway diseases, expression of mucins is increased, which leads to increased morbidity and mortality of the affected patients. However, no study on the effect of cadmium on expression of mucin genes in airway epithelial cells has been reported. Therefore, this study was conducted in order to investigate the effect and the brief signaling pathway of cadmium on expression of mucin genes in human airway epithelial cells. Methods In mucin-producing human NCI-H292 airway epithelial cells and primary cultures of normal nasal epithelial cells, the effect and signaling pathway of cadmium on expression of mucin genes were investigated using reverse transcription–polymerase chain reaction (RT-PCR), real-time PCR, enzyme immunoassay, and immunoblot analysis with several specific inhibitors and small interfering RNA (siRNA). Results Cadmium increased mucin 8 (MUC8) expression and Toll-like receptor (TLR) 4 messenger RNA (mRNA) expression. Cadmium significantly activated phosphorylation of extracellular signal related kinase 1/2 (ERK1/2) mitogen-activated protein kinase (MAPK) and p38 MAPK. ERK1/2 MAPK inhibitor, p38 MAPK inhibitor, TLR4 siRNA, ERK1/2 MAPK siRNA, and p38 MAPK siRNA significantly blocked cadmium-induced MUC8 mRNA expression. TLR4 siRNA significantly blocked cadmium-activated phosphorylation of ERK1/2 MAPK and p38 MAPK. Conclusion The results of this study suggest for the first time that cadmium induces MUC8 expression via TLR4-mediated ERK1/2 and p38 MAPK signaling pathway in human airway epithelial cells.

Background β-Glucan is found in the cell walls of fungi, bacteria, and some plant tissues, and is detected by the innate immune system. Furthermore, this recognition is known to worsen respiratory symptoms in patients with allergic and inflammatory airway diseases. However, the means by which β-glucan affects the secretion of major mucins by human airway epithelial cells has not been elucidated. Therefore, in this study, the effect and signaling pathway of β-glucan on mucins MUC4 and MUC5B were investigated in human airway epithelial cells. Methods In NCI-H292 cells and human normal nasal epithelial cells, the effect and signaling pathway of β-glucan on MUC4 and MUC5B expression were investigated using reverse transcriptase–polymerase chain reaction (RT-PCR), real-time PCR, enzyme immunoassay, and immunoblot analysis with specific inhibitors and small interfering RNA (siRNA). Results β-Glucan increased MUC4 and MUC5B expression and activated the phosphorylation of p38 mitogen-activated protein kinase (MAPK) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB). SB203580 (a p38 MAPK inhibitor) and pyrrolidine dithiocarbamate (PDTC; a NF-κB inhibitor) inhibited β-glucan–induced MUC4 and MUC5B expression. In addition, siRNA knockdown of p38 MAPK blocked β-glucan–induced MUC4 and MUC5B mRNA expression and β-glucan–activated phosphorylation of NF-κB. Furthermore, Toll-like receptor 4 (TLR4) mRNA expression was increased by β-glucan, and siRNA knockdown of TLR4 blocked β-glucan–induced MUC4 and MUC5B mRNA expression and β-glucan–activated phosphorylation of p38 MAPK and NF-κB. Conclusion These results demonstrate that in human airway epithelial cells β-glucan induces MUC4 and MUC5B expression via the TLR4–p38 MAPK–NF-κB signaling pathway.

Garlic has been shown to have antimicrobial, hypolipidemic, antithrombotic, antitumor and immunostimulatory properties. The medicinal effects of garlic are derived from the flavonoid and organosulfur components. Diallyl disulfide (DADS), an organosulfur, is the main component responsible for the diverse biological effects of garlic. However, the effects of DADS on mucin gene expression in airway epithelial cells have not been reported to date. Therefore, this study was performed to investigate the effects and brief signaling pathway of DADS associated with MUC5B expression in NCI-H292 epithelial cells using RT-PCR, ELISA, western blot, immunocytochemistry and cell transfection with siRNA. DADS induced MUC5B expression and activated the phosphorylation of ERK1/2 MAPK. In addition, U0126 inhibited DADS-induced MUC5B expression and DADS-activated phosphorylation of ERK1/2 MAPK. Moreover, the immunopositive cells for MUC5B protein did not appear after treatment of DADS with U0126, and the knockdown of ERK2 MAPK by ERK2 MAPK siRNA significantly blocked DADS-induced MUC5B mRNA expression. However, DADS did not activate the phosphorylation of p38 MAPK, and SB203580 did not inhibit DADS-induced MUC5B expression. This is the first study to show that DADS-induced MUC5B expression appears to be regulated by activation of the ERK2 MAPK signaling pathway in human NCI-H292 airway epithelial cells. Copyright © 2011 John Wiley & Sons, Ltd.

Objectives/Hypothesis: Among the airway mucin genes, the MUC4 gene is an important gene in its response to inflammatory diseases of the upper airway. However, the expression and regulation of the MUC4 gene in the nasal polyps remains unclear. Study Design: The purpose of this study was to evaluate the expression of MUC4 mRNA and synthesis of mucin glycoprotein in the nasal polyps before and after treatment with a topical steroid in vivo and in vitro. Methods: Nasal polyps were obtained from 20 patients with chronic rhinosinusitis and were subsequently cultured. The level of MUC4 mRNA was measured by reverse-transcription polymerase chain reaction, and the amount of the MUC4 mucin glycoprotein was estimated by the enzyme-linked immunosorbent assay method. Results: The expression of MUC4 mRNA was found to be significantly higher in the nasal polyps than in the inferior turbinate (P < .05). The addition of interleukin (IL)-1β and lipopolysaccharide (LPS) increased the expression of MUC4 mRNA and mucin glycoprotein synthesis in cultured nasal polyp epithelial cells. Treatment with glucocorticoid inhibited the expression of MUC4 mRNA in the nasal polyps; it also inhibited the expression of IL-1β and LPS-induced MUC4 mRNA and mucin glycoprotein synthesis in cultured nasal polyp epithelial cells. The inhibitory effects of glucocorticoid were restored by treatment with a glucocorticoid receptor antagonist (RU-486). Conclusions: These results suggest that the MUC4 gene is expressed in the nasal polyps and that glucocorticoid can control the expression of the MUC4 gene and mucin glycoprotein synthesis.

Objective To report clinical characteristics and treatment outcomes of actinomycosis of the paranasal sinus. Study Design Retrospective review. Subjects and Methods The medical records of six patients with actinomycosis of the paranasal sinus between 1998 and 2006 were analyzed. Results There were no immunocompromised patients and all lesions were unilateral. Only one patient had a history of an oroantral fistula due to facial trauma. On CT scan, all patients had unilateral opacification of the maxillary sinus with focal calcified densities. All cases underwent endoscopic sinus surgery followed by relatively short-term antibiotic administration, and there was no recurrence. Conclusions Chronic unilateral maxillary sinusitis, a calcified density in the involved sinus on radiological studies, and unresponsiveness to antibiotics are characteristics of actinomycotic sinusitis. Surgical removal of the involved tissues and the restoration of sinus ventilation seem to be important factors for treating the disease.

Objective: Mucus plays an important role in protecting human airways from external environments by entrapping inhaled foreign particles and bacteria, and clearing them from the airways by ciliary movement. Epigallocatechin-3-gallate (EGCG) is a major component of green tea extract and known to provide numerous functions, such as anti-oxidant effect, anti-tumor effect, anti- diabetic effect, and anti-inflammatory effect. However, the precise mechanism of action about anti-inflammatory effect of EGCG is not fully defined.Method: The effect of EGCG on phorbol 12-myrisate 13- acetate (PMA)–induced MUC5B expression and signaling pathways were investigated in human NCI-H292 airway epithelial cells, human nasal epithelial cells, and in asthma model of mice.Results: PMA-induced MUC5B mRNA and protein levels were significantly decreased after treatment with EGCG. PMA increased phosphorylation of p38 MAPK and this was significantly decreased after pretreatment with EGCG. PMA induced MMP-9 overexpression and this wa...

Objectives/Hypothesis: Leptin is a pleiotropic hormone that regulates food intake and metabolic and endocrine functions. Serum leptin levels have been reported to be increased in patients with allergic rhinitis and nasal polyposis; however, the explanation for this is unclear. We aimed to demonstrate the differential expression of leptin receptors in normal human nasal mucosa and nasal polyps, and to elucidate the effects of leptin on mucin gene expression in human nasal polyp epithelial cells. Study Design: Case-control and in vitro study. Methods: Normal ethmoid sinus mucosa was obtained from 10 subjects and used as a control; nasal polyps were obtained from 10 patients. Leptin receptor expression was analyzed using reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blot analysis. Leptin-induced expression of major respiratory mucins (MUC5AC and MUC5B) in the human nasal polyp epithelial cells was determined using RT-PCR and enzyme-linked immunosorbent assay. Results: The leptin receptor expression was stronger in the nasal polyps than in the normal nasal mucosa. In human nasal polyp epithelial cells, leptin increased the expression of MUC5AC and MUC5B, in a dose- and time-dependent manner, at the gene and protein levels. Leptin-induced mucin expression was inhibited by the leptin receptor antagonist. Conclusions: The increased expression of leptin receptors in nasal polyps implies leptin has a certain role in nasal polyposis. In addition, leptin appears to induce the expression of MUC5AC and MUC5B through leptin receptors in the human nasal polyp epithelial cells. Laryngoscope, 2010