Excessive Mucus Production Research Articles

How does rhinovirus cause the common cold cough?

Cough is a protective reflex to prevent aspiration and can be triggered by a multitude of stimuli. The commonest form of cough is caused by upper respiratory tract infection and...

Interventions for enhancing adherence to treatment in adults with bronchiectasis.

Bronchiectasis is characterised by a widening of the airways, leading to excess mucus production and recurrent infection. It is more prevalent in women and those in middle age. Many patients with bronchiectasis do not adhere to treatments (medications, exercise and airway clearance) prescribed for their condition. The best methods to change these adherence behaviours have not been identified. To assess the effects of interventions to enhance adherence to any aspect of treatment in adults with bronchiectasis in terms of adherence and health outcomes, such as pulmonary exacerbations, health-related quality of life and healthcare costs. We searched the Cochrane Airways Group Specialised Register (CAGR), which contains trial reports identified through systematic searches of CENTRAL, MEDLINE, EMBASE, CINAHL, AMED and PsycINFO, from inception to October 2015. We planned to include randomised controlled trials (RCTs) of adults with bronchiectasis that compared any intervention aimed at enhancing adherence versus no intervention, usual care or another adherence intervention. We excluded studies of those who had bronchiectasis due to cystic fibrosis. Two review authors (AMcC and ET) independently screened titles, abstracts and full-texts of identified studies. Searches retrieved 36 studies reported in 37 articles; no eligible studies were identified. We did not identify any studies that assessed the effect of interventions to enhance adherence to treatment in bronchiectasis. Adequately powered, well-designed trials of adherence interventions for bronchiectasis are needed.

Differential Gene Expression Profiles and Selected Cytokine Protein Analysis of Mediastinal Lymph Nodes of Horses with Chronic Recurrent Airway Obstruction (RAO) Support an Interleukin-17 Immune Response.

Recurrent airway obstruction (RAO) is a pulmonary inflammatory condition that afflicts certain mature horses exposed to organic dust particulates in hay. Its clinical and pathological features, manifested by reversible bronchoconstriction, excessive mucus production and airway neutrophilia, resemble the pulmonary alterations that occur in agricultural workers with occupational asthma. The immunological basis of RAO remains uncertain although its chronicity, its localization to a mucosal surface and its domination by a neutrophilic, non-septic inflammatory response, suggest involvement of Interleukin-17 (IL-17). We examined global gene expression profiles in mediastinal (pulmonary-draining) lymph nodes isolated from RAO-affected and control horses. Differential expression of > 200 genes, coupled with network analysis, supports an IL-17 response centered about NF-κB. Immunohistochemical analysis of mediastinal lymph node sections demonstrated increased IL-17 staining intensity in diseased horses. This result, along with the finding of increased IL-17 concentrations in lymph node homogenates from RAO-affected horses (P = 0.1) and a down-regulation of IL-4 gene and protein expression, provides additional evidence of the involvement of IL-17 in the chronic stages of RAO. Additional investigations are needed to ascertain the cellular source of IL-17 in this equine model of occupational asthma. Understanding the immunopathogenesis of this disorder likely will enhance the development of therapeutic interventions beneficial to human and animal pulmonary health.

Pathology of Edwardsiella tarda infection in African catfish, Clarias gariepinus (Burchell 1822), fingerlings

Abstract Edwardsiella tarda is one of the serious fish pathogens infecting both cultured and wild fish species. This study aimed to assess the phenotypic characterization and pathogenicity of E. tarda isolated from Clarias gariepinus (Burchell) with dropsy and histopathological alterations. The causative agent was identified with Vitek 2, and its pathogenicity was determined by intramuscular injection. The challenged catfish exhibited vertical hanging, frothing, excess mucus production, listing, swollen abdomen, anorexia, fin and tail rot, and reddish operculum. The LD50 of E. tarda PBB and PBP strains was found to be 8.52 × 106 and 1.68 × 107 cells fish-1, respectively. Histopathological observations on catfish infected naturally revealed lymphocyte infiltration in muscle and focal necrosis, hyperplasia, edema, and swelling of the gill lamellar epithelium. The kidney of diseased fish exhibited ischemic type tubulopathy, necrosis of nephritic tubules, hyperplastic hematopoietic tissue, rupture of the tubular basement membrane, hydropic dystrophy of nephritic cells, neutrophil infiltration, fibrinoid necrosis of nephretic tubules, hemosiderin deposition, and edema. The liver sections revealed lymphocyte infiltration, dilation of hepatic sinusoids, expansion of space between hepatic sinusoids, and focal necrosis. The inflammatory responses observed in kidney and liver in the present study were presumably suppuration and were attributed to the potential virulence factors of E. tarda.

Pharmacotherapy for the treatment of asthma: current treatment options and future directions

Asthma is a prevalent disease characterized by chronic inflammatory changes of the airway and marked by airway hyperresponsiveness, edema, and excess mucus production. Management of the disease has focused upon reversing the early airway changes and limiting the late effects of airway remodeling. Several classes of medications are available for the effective treatment and long-term control of asthma and novel therapeutic options are in development that hold promise in improving patient outcome. A review of updated guidelines and current literature was conducted to identify available pharmacologic treatments of asthma and determine future directions in development of novel therapeutic options. Inhaled corticosteroids are the most effective medications in long-term asthma control with adjunct medications such as β2-agonists, which can provide symptomatic relief. Other classes of asthma control medications including anticholinergics, cromolyns, and leukotriene receptor modifiers can also be used to develop an effective management strategy based on asthma severity. Several classes of medications are available for the effective management of asthma. Inhaled corticosteroids play a central role in control of inflammation and several other adjuncts are available to tailor therapy to the patient's symptoms. New therapeutic options that target downstream inflammatory mediators can provide increased efficacy while limiting side effects.

Acute cigarette smoke accelerate chronic bronchitis development in ENaC overexpressing newborn-mice

Chronic bronchitis (CB) is characterized by mucus accumulation, airway neutrophilia, and chronic airway obstruction. Excess mucus production, together with less efficient cough and loss of normal ciliary function, leads to recurrent respiratory obstruction. Overexpression of Na+ ion channels (bENaC) in the airway epithelial membrane of mice leads to airway surface liquid depletion and mucocilia clearance dysfunction, resulting in airway mucus accumulation and subsequent COPD-like disease (Mall et al. AJRCCM 2008). Cigarette smoke (CS) exposure is the major factor that causes non-infectious chronic bronchitis. Therefore, we hypothesize that cigarette smoke exposure induces mucus production and inflammation which enhances the progression of obstructive bronchitis development in bENaC mice.

Cigarette smoke exposure enhances obstructive bronchitis in ENaC overexpressing newborn-mice

Chronic bronchitis (CB) is characterized by mucus accumulation, airway neutrophilia, and chronic airway obstruction. Excess mucus production, together with less efficient cough and loss of normal ciliary function, leads to recurrent airflow limitation, airway remodeling and respiratory obstruction. Overexpression of Na+ ion channels (βENaC) in the airway epithelial membrane of mice leads to airway surface liquid depletion and mucocilia clearance dysfunction, resulting in airway mucus accumulation and subsequent COPD-like disease (Mall et al. AJRCCM 2008). Cigarette smoke exposure is recognized to be the major factor that causes non-infectious chronic bronchitis. Therefore, we hypothesize that cigarette smoke exposure induces mucus production and inflammation which enhances the progression of obstructive bronchitis development in βENaC mice.

Extravasation mucocele arising from a lingual thyroglossal duct remnant.

Although a thyroglossal duct cyst is a congenital anomaly, it can also appear in adults. Despite the presence of embryological remnants, it is still unclear why the cyst should suddenly develop later in life. We report a case of a 46-year-old male with an extravasation mucocele arising from a long-standing lingual thyroglossal duct remnant. MRI demonstrated a lingual cystic lesion near the hyoid bone associated with a suprahyoid tract-like structure masquerading as a thyroglossal duct cyst. However, histopathological examination demonstrated a mucocele secondary to a rupture of a thyroglossal duct remnant with numerous intramural heterotopic salivary glands. We propose a new mechanism of an acquired cystic formation of this congenital disease that excessive production of mucus from heterotopic salivary glands and a physical trauma such as swallowing may lead to extravasation of mucus from the thyroglossal duct.

Expression and Regulation of Transcription Factor FoxA2 in Chronic Rhinosinusitis With and Without Nasal Polyps.

PurposeChronic rhinosinusitis (CRS) is characterized by the excessive production of mucus. However, the molecular mechanism underlying mucin overproduction in CRS with or without nasal polyps (CRSwNP and CRSsNP, respectively) is poorly understood. This study was conducted to assess the importance of the transcription factor FoxA2 in mucin production and to investigate the targeting of FoxA2 as a potential therapeutic strategy for mucus hypersecretion in CRS patients.MethodsWe enrolled 15 CRSwNP patients, 15 CRSsNP patients, and 10 normal controls in this study. The expression levels of FoxA2, MUC5AC, and MUC5B in inflamed and healthy nasal tissues were examined via immunohistochemistry and quantitative reverse transcription-polymerase chain reaction, and the levels of several proinflammatory cytokines in nasal secretions were measured via FlowCytomix analysis. In addition, the expression of MUC5AC and FoxA2 was determined in polyp-derived epithelial cells and NCI-H292 cells after in vitro stimulation.ResultsFoxA2 was significantly down-regulated, and MUC5AC and MUC5B were significantly up-regulated in both the CRSwNP and CRSsNP patients compared to the controls (P<0.05), and the protein level of FoxA2 was negatively associated with the IL-6 level in the CRS patients (P<0.05). IL-6 significantly increased MUC5AC expression but inhibited FoxA2 expression in vitro (P<0.05). Transfection with a FoxA2 expression plasmid significantly decreased MUC5AC promoter activity (P<0.05) and inhibited IL-6-induced MUC5AC production (P<0.05). In addition, clarithromycin significantly alleviated IL-6-induced FoxA2 suppression and decreased MUC5AC expression in vitro (P<0.05).ConclusionsOur findings suggest that FoxA2 may be considered a therapeutic target for the modulation of mucus hypersecretion in CRS patients.

Growth rates and ages of deep-sea corals impacted by the Deepwater Horizon oil spill

The impact of the April 2010 Deepwater Horizon (DWH) spill on deep-sea coral communities in the Gulf of Mexico (GoM) is still under investigation, as is the potential for these communities to recover. Impacts from the spill include observation of corals covered with flocculent material, with bare skeleton, excessive mucous production, sloughing tissue, and subsequent colonization of damaged areas by hydrozoans. Information on growth rates and life spans of deep-sea corals is important for understanding the vulnerability of these ecosystems to both natural and anthropogenic perturbations, as well as the likely duration of any observed adverse impacts. We report radiocarbon ages and radial and linear growth rates based on octocorals (Paramuricea spp. and Chrysogorgia sp.) collected in 2010 and 2011 from areas of the DWH impact. The oldest coral radiocarbon ages were measured on specimens collected 11km to the SW of the oil spill from the Mississippi Canyon (MC) 344 site: 599 and 55calyr BP, suggesting continuous life spans of over 600 years for Paramuricea biscaya, the dominant coral species in the region. Calculated radial growth rates, between 0.34μmyr−1 and 14.20μmyr−1, are consistent with previously reported proteinaceous corals from the GoM. Anomalously low radiocarbon (Δ14C) values for soft tissue from some corals indicate that these corals were feeding on particulate organic carbon derived from an admixture of modern surface carbon and a low 14C carbon source. Results from this work indicate fossil carbon could contribute 5–10% to the coral soft tissue Δ14C signal within the area of the spill impact. The influence of a low 14C carbon source (e.g., petro-carbon) on the particulate organic carbon pool was observed at all sites within 30km of the spill site, with the exception of MC118, which may have been outside of the dominant northeast–southwest zone of impact. The quantitatively assessed extreme longevity and slow growth rates documented here highlight the vulnerability of these long-lived deep sea coral species to disturbance.

Identifikasi Koi Herpesvirus pada Dosis yang Berbeda dengan Metode Imunohistokimia Streptavidin Biotin pada Ikan Nila (Oreochromis niloticus) &lt;br&gt;&lt;i&gt;[Identification of Koi Herpes Virus At Different Dose with Streptavidin Biotin Methods Immunohistochemistry on Tilapia (Oreochromis niloticus)]&lt;i&gt;

Abstract KHV is a viral disease in goldfish and Koi Fish (Cyprinus carpio) is a highly contagious, infecting all ages or sizes of fish and aquaculture systems. This disease results in mortality between 80% - 100% of the total fish population, with an incubation period of between 1-7 days. KHV infection triggered by a drop in ambient temperature so it is referred to as a virus that attacks when cold (a cold virus). The disease attacks the temperature range of 18-28 ° C and can cause death. This virus attacks can occur at any age of the fish ranging in size from the seed to the parent. The most prominent clinical symptoms due to KHV infection is the sudden death 1-2 days after infection. Other clinical symptoms are necrosis of the gills, sunken eyes, bleeding at the gills, hemorraghe, excess mucus production in the body, and secondary bacterial infections or parasitic infestations. Streptavidin biotin immunohistochemical method was applied to the study of cells and tissues by staining imunostaining. Technique of determining the existence of (location) antigen (target protein) in tissue using antigen-antibody reaction that begins with histotenik procedure is the procedure of making tissue sections (histology). This method has high sensitivity and fast so that it can be applied to the detection of KHV antigen in tissues of fish Tilapia (Orechromis niloticus). This study aims to determine the presence of KHV antigen in tilapia gills after infection. The method used in this study is the experimental method. Dose of virus titer used was 1 ID50, ID50 10, 100 ID50, ID50 1000. The results showed that the Streptavidin Biotin immunohistochemical examination imunopatologi able to detect KHV virus Ag in the gill tissue of tilapia (Oreochromis niloticus) were infected with different doses. In all treatments showed on all the gills are KHV antigen is indicated by the presence of a golden brown color on the gill epithelium. Advised Streptavidin biotin immunohistochemistry test was applied to the detection of the presence or absence of fish-carp KHV carrier as a routine control program and control, including the prevention and outbreak of KHV in Indonesia, because of KHV were attacked in tilapia was persistent and did not show clinical symptoms

Equine Recurrent Airway Obstruction

Abstract Equine Recurrent Airway Obstruction (RAO), also known as heaves or broken wind, is one of the most common disease in middle-aged horses. Inflammation of the airway is inducted by organic dust exposure. This disease is characterized by neutrophilic inflammation, bronchospasm, excessive mucus production and pathologic changes in the bronchiolar walls. Clinical signs are resolved in 3-4 weeks after environmental changes. Horses suffering from RAO are susceptible to allergens throughout their lives, therefore they should be properly managed. In therapy the most importanthing is to eliminate dust exposure, administration of corticosteroids and use bronchodilators to improve pulmonary function.

Inhaled mannitol for non-cystic fibrosis bronchiectasis: a randomised, controlled trial.

Bronchiectasis is characterised by excessive production of mucus and pulmonary exacerbations. Inhaled osmotic agents may enhance mucociliary clearance, but few long-term clinical trials have been conducted. To determine the impact of inhaled mannitol on exacerbation rates in patients with non-cystic fibrosis (CF) bronchiectasis. Secondary endpoints included time to first exacerbation, duration of exacerbations, antibiotic use for exacerbations and quality of life (QOL) (St George's Respiratory Questionnaire, SGRQ). Patients with non-CF bronchiectasis and a history of chronic excess production of sputum and ≥2 pulmonary exacerbations in the previous 12 months were randomised (1:1) to 52 weeks treatment with inhaled mannitol 400 mg or low-dose mannitol control twice a day. Patients were 18-85 years of age, baseline FEV1 ≥40% and ≤85% predicted and a baseline SGRQ score ≥30. 461 patients (233 in the mannitol and 228 in the control arm) were treated. Baseline demographics were similar in the two arms. The exacerbation rate was not significantly reduced on mannitol (rate ratio 0.92, p=0.31). However, time to first exacerbation was increased on mannitol (HR 0.78, p=0.022). SGRQ score was improved on mannitol compared with low-dose mannitol control (-2.4 units, p=0.046). Adverse events were similar between groups. Mannitol 400 mg inhaled twice daily for 12 months in patients with clinically significant bronchiectasis did not significantly reduce exacerbation rates. There were statistically significant improvements in time to first exacerbation and QOL. Mannitol therapy was safe and well tolerated. NCT00669331.

Targeting pro-resolution pathways to combat chronic inflammation in COPD.

Chronic obstructive pulmonary disease (COPD) is an inflammatory lung condition that is associated with irreversible airflow obstruction as a consequence of small airways disease, excessive mucus production and emphysema. Paradoxically, excessive inflammation fails to control microbial pathogens that not only colonise COPD airways, but also trigger acute exacerbations, which markedly increase inflammation underlying host tissue damage. Excessive production of leukocyte mobilising cytokines such as CXCL8 (IL-8) and leukotriene B4 (LTB4) in response to environmental stimuli (cigarette smoke and microbial products) are thought to maintain chronic inflammation, in conjunction with inefficient macrophage clearance of microbes and apoptotic neutrophils. In this perspective, we discuss an alternative view on why inflammation persists with a focus on why pro-resolution mediators such as lipoxin A4 (LXA4), D-series resolving and Annexin A1 fail to effectively switch off inflammation in COPD. These pro-resolving mediators converge on the G-protein coupled receptor, ALX/FPR2. This receptor is particularly relevant to COPD as the complex milieu of exogenous and host-derived mediators within the inflamed airways include agonists that potently activate ALX/FPR2, including Serum Amyloid A (SAA) and the cathelicidin, LL-37. There is emerging evidence to suggest that ALX/FPR2 can exist in alternative receptor conformations in an agonist-biased manner, which facilitates alternate functional receptor behaviors. Hence, the development of more stable pro-resolving analogs provides therapeutic opportunities to address ALX/FPR2 conformations to counteract pathogenic signaling and promote non-phlogistic clearance pathways essential for resolution of inflammation.

Differentially expressed proteins in gill and skin mucus of Atlantic salmon (Salmo salar) affected by amoebic gill disease

The external surfaces of fish, such as gill and skin, are covered by mucus, which forms a thin interface between the organism and water. Amoebic gill disease (AGD) is a parasitic condition caused by Neoparamoeba perurans that affects salmonids worldwide. This disease induces excessive mucus production in the gills. The host immune response to AGD is not fully understood, and research tools such as genomics and proteomics could be useful in providing further insight. Gill and skin mucus samples were obtained from Atlantic salmon (Salmo salar) which were infected with N. perurans on four successive occasions. NanoLC tandem mass spectrometry (MS/MS) was used to identify proteins in gill and skin mucus of Atlantic salmon affected by AGD. A total of 186 and 322 non-redundant proteins were identified in gill and skin mucus respectively, based on stringent filtration criteria, and statistics demonstrated that 52 gill and 42 skin mucus proteins were differentially expressed in mucus samples from AGD-affected fish. By generating protein–protein interaction networks, some of these proteins formed part of cell to cell signalling and inflammation pathways, such as C-reactive protein, apolipoprotein 1, granulin, cathepsin, angiogenin-1. In addition to proteins that were entirely novel in the context in the host response to N. perurans, our results have confirmed the presence of protein markers in mucus that have been previously predicted on the basis of modified mRNA expression, such as anterior gradient-2 protein, annexin A-1 and complement C3 factor. This first proteomic analysis of AGD-affected salmon provides new information on the effect of AGD on protein composition of gill and skin mucus. Future research should focus on better understanding of the role these components play in the response against infection with N. perurans.

Targeting Mucus Hypersecretion: New Therapeutic Opportunities for COPD?

Airway mucus has a key role in protective innate immune responses, but excessive mucus production and secretion in proximal and in distal airways are associated with disabling symptoms (cough and sputum), lung function decline, exacerbations and mortality in patients with chronic obstructive pulmonary disease (COPD). Cellular and molecular mechanisms leading to mucin production and secretion have largely been identified using cultured epithelial cells and animal models. Cigarette smoke and microbial products are potent triggers of mucin production, which involves recognition of specific molecular patterns by cognate receptors and activation of metalloproteases at the epithelial cell surface, leading to epidermal growth factor receptor activation and mucin mRNA and protein synthesis. After mucin synthesis has occurred, mucins are tightly packed into intracytoplasmic granules. Many stimuli induce secretion of mucin granules from epithelial cells, but neutrophil serine proteases are the most potent inducers of mucin secretion. Neutrophils recruited to the airway epithelium also promote mucin production via neutrophil proteases and oxidative stress. Several drugs currently available for the treatment of COPD patients reduced mucus hypersecretion in preclinical models relevant to COPD, but their effects on mucus hypersecretion in humans have not been assessed. Testing the effects of these drugs and of novel molecules designed for reducing mucus production and/or secretion will require performing specifically designed clinical trials. These trials will be necessary to explore the hypothesis that reducing mucus hypersecretion is beneficial in COPD patients.

Hypoxia-mediated mechanism of MUC5AC production in human nasal epithelia and its implication in rhinosinusitis.

BackgroundExcessive mucus production is typical in various upper airway diseases. In sinusitis, the expression of MUC5AC, a major respiratory mucin gene, increases. However, the mechanisms leading to mucus hypersecretion in sinusitis have not been characterized. Hypoxia due to occlusion of the sinus ostium is one of the major pathologic mechanisms of sinusitis, but there have been no reports regarding the mechanism of hypoxia-induced mucus hypersecretion.Methods and FindingsThis study aims to identify whether hypoxia may induce mucus hypersecretion and elucidate its mechanism. Normal human nasal epithelial (NHNE) cells and human lung mucoepidermoid carcinoma cell line (NCI-H292) were used. Sinus mucosa from patients was also tested. Anoxic condition was in an anaerobic chamber with a 95% N2/5% CO2 atmosphere. The regulatory mechanism of MUC5AC by anoxia was investigated using RT-PCR, real-time PCR, western blot, ChIP, electrophoretic mobility shift, and luciferase assay. We show that levels of MUC5AC mRNA and the corresponding secreted protein increase in anoxic cultured NHNE cells. The major transcription factor for hypoxia-related signaling, HIF-1α, is induced during hypoxia, and transfection of a mammalian expression vector encoding HIF-1α results in increased MUC5AC mRNA levels under normoxic conditions. Moreover, hypoxia-induced expression of MUC5AC mRNA is down-regulated by transfected HIF-1α siRNA. We found increased MUC5AC promoter activity under anoxic conditions, as indicated by a luciferase reporter assay, and mutation of the putative hypoxia-response element in MUC5AC promoter attenuated this activity. Binding of over-expressed HIF-1α to the hypoxia-response element in the MUC5AC promoter was confirmed. In human sinusitis mucosa, which is supposed to be hypoxic, expression of MUC5AC and HIF-1α is higher than in control mucosa.ConclusionThe results indicate that anoxia up-regulates MUC5AC by the HIF-1α signaling pathway in human nasal epithelia and suggest that hypoxia might be a pathogenic mechanism of mucus hypersecretion in sinusitis.

Acute dermatitis in farmed trout: an emerging disease

A new skin condition, known as puffy skin disease (PSD), emerged in farmed rainbow trout Oncorhynchus mykiss (Walbaum) in 2002. The number of new cases increased considerably from 2006. Clinical signs include white or grey skin patches, which become raised and red with excessive mucous production and scale loss. Fish are inappetant and lose condition. Histologically, the key feature is epithelial hyperplasia. We undertook a questionnaire study of trout farmers in England and Wales to investigate prevalence and risk factors. PSD was reported on 37% (n = 49) of rainbow trout sites, located in 28 river catchments. The increase in cases from 2006 onwards was mirrored by the increase in red mark syndrome (RMS). Prevalence and severity of PSD were highest in the summer months. The presence of PSD was associated with RMS (OR = 9.7, P < 0.001). Sites receiving live rainbow trout in the previous 12 months were considerably more likely to have PSD (OR = 5.3. P < 0.01), which suggests an infectious aetiology. The size of affected fish and prevalence varied between farms, indicating that farm-level factors are important. Future research should further investigate the aetiology of PSD and practices to manage the disease.

Melatonin inhibits MUC5AC production via suppression of MAPK signaling in human airway epithelial cells

Mucus acts as a primary defense system in the airway against various stimuli. However, excess mucus production causes a reduction in lung function via limitation of the airflow in the airway of patients suffering from asthma or chronic obstructive pulmonary disease (COPD). In this study, we evaluated the effects of melatonin on the production of MUC5AC, a major constituent of the mucin that is secreted from the airway, using epidermal growth factor (EGF)-stimulated NCI-H292 cells, a human mucoepidermoid carcinoma cell line, and an ovalbumin (OVA)-induced asthma murine model. Melatonin treatment significantly reduced the mRNA and protein levels of MUC5AC and reduced interleukin (IL)-6 production in EGF-stimulated H292 cells. Melatonin markedly decreased the phosphorylation of MAPKs, including ERK1/2, JNK, and p-38, induced by EGF stimulation. These findings were consistent with the results using MAPK inhibitors. Particularly, co-treatment with melatonin and a MAPK inhibitor more effectively suppressed MAPK phosphorylation than treatment with a MAPK inhibitor alone, which resulted in a reduction in MUC5AC expression. In the asthma murine model, melatonin-treated mice exhibited a marked reduction in MUC5AC expression in the airway compared with the OVA-induced mice. These reductions were accompanied by reductions in proinflammatory cytokine production and inflammatory cell infiltration. Collectively, these findings indicate that melatonin effectively inhibits MUC5AC expression. These effects may be closely associated with the inhibition of MAPK phosphorylation. Furthermore, our study suggests that melatonin could represent a potential therapeutic for chronic airway diseases, such as asthma and COPD.

Modulation of expression in BEAS-2B airway epithelial cells of α-l-fucosidase A1 and A2 by Th1 and Th2 cytokines, and overexpression of α-l-fucosidase 2

Chronic Th2-driven airway inflammation with excessive mucus production occurs in asthma. The regulation of FUCA1 and FUCA2 gene expression and enzyme activity in response to asthma-associated Th2 cytokines and, for contrast, Th1 cytokine IFN-γ, were investigated in a human airway cell line. BEAS-2B cells were supplemented with Th2-derived cytokines (IL-13, IL-4, IL-5) or/and IFN-γ. RNA and cell supernatants from stimulated and unstimulated cells were collected over a period of 3 h. Alpha-L-fucosidase A1 and A2 gene expression were assessed using real time RT-PCR, while enzymatic activities were measured using a fluorescent assay. To characterise α-L-fucosidase A2, CHO-K1 and BEAS-2B cell lines were transiently transfected, the FUCA2 gene was overexpressed, and the protein was immunoprecipitated. The transcription of FUCA1 was upregulated (p < 0.01) in response to IFN-γ, suggesting that FUCA1 transcription and fucosidase activity are regulated in a Th1-dependent manner. The gene expression was the highest for 30 min after IFN-γ stimulation (>twofold induction), whereas secreted enzyme activity in BEAS-2B cells was significantly increased 1 h after IFN-γ addition. IL-4, IL-5 and IL-13 had no effect on FUCA1 and FUCA2 expression and activity. The IFN-γ-induced increase in expression and activity was repressed by the presence of the Th2 cytokine IL-5. Enzymatically active α-L-fucosidase 2 was immunoprecipitated from BEAS-2B cells, with highest activity at pH 4.9. IL-13, IL-4 and IL-5 have no effect on the expression of FUCA1 and FUCA2, but its expression is upregulated by IFN-γ, a Th1 cytokine. Active α-L-fucosidase 2 was overexpressed in BEAS-2B cells.