Intranasal steroids decrease eosinophils but not mucin expression

Cardiovascular Research Institute, Box 0130, University of California San Francisco, San Francisco, CA 94 143-0130, USA.
European Respiratory Journal (Impact Factor: 7.64). 11/2004; 24(4):594-600. DOI: 10.1183/09031936.04.00014404
Source: PubMed


Increased mucin expression is a feature of nasal polyposis. Corticosteroids reduce polyp size and symptoms, but their effect on mucin production remains unknown. In this study, the effects of intranasal corticosteroids on MUC5AC mucin expression, nasal resistance, eosinophil and neutrophil infiltration, epidermal growth factor receptor (EGFR), interleukin (IL)-8, and tumour necrosis factor (TNF)-alpha expression was assessed in nasal polyps. In nine subjects, one nasal polyp was removed surgically before treatment and another was removed after 8 weeks of intranasal fluticasone (400 Tissues were processed for in situ hybridisation and immunohistochemical staining. Described effects of fluticasone on nasal polyps (reduction in nasal resistance and in eosinophil infiltration) were evaluated. Morphometric analysis was performed to assess the effect of fluticasone on epithelial-, MUC5AC-, EGFR- and IL-8-stained areas, TNF-alpha-stained cells, and neutrophil numbers. Treatment with fluticasone decreased nasal resistance and intra-epithelial eosinophils. The MUC5AC-stained area in the epithelium was unchanged by treatment; MUC5AC mRNA expression was unaffected by treatment. EGFR-stained area, intra-epithelial neutrophil numbers, IL-8 and TNF-alpha expression were also unchanged by therapy. Intranasal fluticasone was effective in decreasing nasal airflow resistance and intra-epithelial eosinophils but had no effect on mucin or epidermal growth factor receptor expression or on neutrophil recruitment.

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    • "The same study also demonstrated that apigenin-mediated MUC1 downregulation was associated with increased apoptosis and decreased clonogenic potential. EGF through EGFR signaling stimulates MUC5AC expression in a human airway epithelial cell line [98] and its hypersecretion is associated with severe pulmonary disorders like asthma, chronic bronchitis, cystic fibrosis and bronchiectasis [99]. Apigenin treatment was shown to decrease both de novo [100] as well as EGF-induced MUC5AC expression [100] in lung cancer NCI-H292 cells. "
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    ABSTRACT: Deregulated mucin expression is a hallmark of several inflammatory and malignant pathologies. Emerging evidence suggests that, apart from biomarkers, these deregulated mucins are functional contributors to pathogenesis in inflammation and cancer. Both overexpression and downregulation of mucins in various organ systems is associated with pathobiology of inflammation and cancer. Restoration of mucin homeostasis has become an important goal for therapy and management of such disorders and has fueled the quest for selective mucomodulators. With improved understanding of mucin regulation and mechanistic insights into their pathobiological roles, there is optimism to find selective non-toxic agents capable of modulating mucin expression and function. Recently, natural compounds derived from dietary sources have drawn attention due to their anti-inflammatory and anti-oxidant properties and low toxicity. Considerable efforts have been directed towards evaluating dietary natural products as chemopreventive and therapeutic agents; identification, characterization and synthesis of their active compounds; and improving their delivery and bioavailability. We describe the current understanding of mucin regulation, rationale for targeting mucins with natural products and discuss some natural products that modulate mucin expression and functions. We further discuss the approaches and parameters that should guide future research to identify and evaluate selective natural mucomodulators for therapy.
    Cancer Treatment Reviews 01/2015; 41(3). DOI:10.1016/j.ctrv.2015.01.001 · 7.59 Impact Factor
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    • "The advent of topically administered corticosteroids has improved the treatment of upper (NP and rhinitis) and lower (asthma, chronic obstructive airways disease) airways disease (Fokkens et al 2007). Their clinical efficacy is achieved by a combination of anti inflammatory effects along with their ability to reduce airway eosinophillic infiltration by preventing their increased viability and activation (Burgel et al 2004). Both topical and systemic glucocorticoids may affect the eosinophil function by both directly reducing eosinophil viability and function or indirectly reducing the secretion of chemotactic cytokines by nasal mucosa and polyp epithelial cells (Roca-Ferrer et al 1997). "
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    ABSTRACT: Nasal polyps are common, affecting up to four percent of the population. Their etiology remains unclear, but they are known to have associations with allergy, asthma, infection, cystic fibrosis, and aspirin sensitivity. They present with nasal obstruction, anosmia, rhinorrhoea, post nasal drip, and less commonly facial pain. Clinical examination reveals single or multiple grey polypoid masses in the nasal cavity. Computerized tomography allows evaluation of the extent of the disease and is essential if surgical treatment is to be considered. Management of polyposis involves a combination of medical therapy and surgery. There is good evidence for the use of corticosteroids (systemic and topical) both as primary treatment and as postoperative prophylaxis against recurrence. Surgical treatment has been refined significantly over the past twenty years with the advent of endoscopic sinus surgery and, in general, is reserved for cases refractory to medical treatment. Recurrence of the polyposis is common with severe disease recurring in up to ten percent of patients.
    Therapeutics and Clinical Risk Management 05/2008; 4(2):507-12. · 1.47 Impact Factor
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    ABSTRACT: The definition, pathophysiology and surgical approach of nasal polyposis (NP) are still under debate. In this chapter, NP is considered as a chronic inflammatory disease of the ethmoidal sinus mucosa characterised on nasal endoscopic examination by the presence, bilaterally, of non-infected white-oedematous polyps originating into the ethmoidal labyrinths and most of the time, arising from the middle and/or superior meatus and/or the sphenoethmoidal recess. This definition is aimed at stressing that NP is a specific disease that can easily be recognised among all other forms of rhinosinusitis and other nasal diseases. Our opinion is that sinus ventilation/drainage or obstruction in the ostio-meatal complex is a minor pathogenic factor in NP disease. Our hypothesis is that NP is a disease generated by remnants of vestigial olfactory mucosa scattered in the ethmoidal sinuses. Only people who have remnants develop NP. This vestigial olfactory mucosa has probably lost its histological features, but has kept some biological properties, among which is the ability to attract eosinophils. Olfaction is probably one of the oldest phylogenetic senses and eosinophils are probably one of the oldest cells of the innate immune system. Our hypothesis is that NP could be regarded as an inflammatory disease resulting from a dysfunction of the innate immune system associated to the olfactory organ. In this concept, the role of surgery for NP is to remove as much as possible of the vestigial ethmoidal mucosa. The role of the sinuses is still unclear and the need to retain more or less of the compartmentalisation of the ethmoidal labyrinths is also questionable. Our hypothesis is that, when dealing with the NP disease, complete removal of the bony lamellas partitioning the ethmoidal labyrinth is not more harmful than trying to restore ventilation/drainage in the different ethmoidal compartments. The combination of both hypotheses led us to propose the nasalisation procedure as a surgical approach for NP. The aim of the nasalisation procedure is to remove the ethmoidal mucosa as completely as possible without hazards, and to transform the ethmoidal labyrinth into a unique cavity opening into the nose (nasalisation). To achieve the nasalisation procedure, it is more important to know the anatomy of the ethmoidal walls than the compartmentalisation inside the ethmoidal labyrinth.The technical key point to safely perform a nasalisation procedure is to gently strip the mucosa to follow the bony structure of the medial orbital wall, ethmoidal roof and conchal lamina. Our results show that NP is a chronic disease which cannot be cured, but that the underlying chronic eosinophilic ethmoiditis disease seems to be better controlled after nasalisation than after ethmoidectomy. When the medical treatment with corticosteroids fails to stop the eosinophil attraction, the aim of surgery should be to remove as completely as possible the ethmoidal mucosa, which seems to be the main attractant for eosinophils.
    Nasal Polyposis, 01/1970: pages 265-274;
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