LTD4 and TGF-β1 induce the expression of metalloproteinase-1 in chronic rhinosinusitis via a cysteinyl leukotriene receptor 1-related mechanism

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Bone: the final frontier for Staphylococcus aureus penetration in chronic rhinosinusitis

The superantigenic properties of Staphylococcus aureus have been implicated in increasing the inflammatory process in airway diseases. Local formation of IgE antibodies against staphylococcal enterotoxins by secondary lymphoid tissue in nasal polyps has been demonstrated. Staphylococcus aureus is known to colonize the nasal mucosa, and has been found invading the nasal submucosa and intracellularly.Objective: To evaluate the limits of Staphylococcus aureus invasion in the upper airway.Material and methods: Inferior turbinate samples from 3 patients without sinus disease, 6 ethmoid samples from patients with chronic rhinosinusitis with nasal polyposis, and 6 ethmoid samples from patients with chronic rhinosinusitis without nasal polyposis were studied. A fluorescein-labeled PNA probe against Staphylococcus aureus was used to test for the presence of the bacterium in bone (after decalcification) and mucosa.Results: We found Staphylococcus aureus invading the nasal submucosa in patients with nasal polyposis, but no cases of Staphylococcus aureus positivity in bone. in conclusion, we cannot support the hypothesis of nasal bone as a reservoir for Staphylococcus aureus, releasing massive amounts of staphylococcal enterotoxins and eliciting an inflammatory reaction, as occurs with the nasal mucosa.Univ São Paulo, Dept Otorhinolaryngol, São Paulo, BrazilSão Paulo State Mil Police, Mil Police Hosp, São Paulo, BrazilFed Univ São Paulo Unifesp, Dept Otorhinolaryngol, São Paulo, BrazilFed Univ São Paulo Unifesp, Dept Immunol, São Paulo, BrazilFed Univ São Paulo Unifesp, Dept Otorhinolaryngol, São Paulo, BrazilFed Univ São Paulo Unifesp, Dept Immunol, São Paulo, BrazilWeb of Scienc

Epithelium and stroma from nasal polyp mucosa exhibits inverse expression of TGF- beta(1) as compared with healthy nasal mucosa

Objective: To evaluate TGF-beta(1) expression in polypoid mucosa (epithelium and stroma) of patients with chronic rhinosinusitis with nasal polyposis (CRSwNP).Methods: Cross-sectional study with two groups: 17 patients with nasal polyposis and 11 controls. Polyps and normal nasal mucosa were processed by immunohistochemical methods for TGF-beta 1 visualization. Then, the percentage of TGF-beta 1 expression in stroma and epithelium was objectively quantified using UT Morph software.Results: A lower percentage of positive expression was found in the epithelium of CRSwNP patients (32.44%) versus normal controls (55.91%) (p < 0.05), and a higher percentage of positive expression in the stroma of CRSwNP patients (23.24%) versus controls (5.88%) (p < 0.05).Conclusion: the lower percentage of TGF-beta(1) expression in the nasal epithelium of CRSwNP patients may have an impact on epithelium-directed topical treatments employed in this patient population.Universidade Federal de São Paulo, Dept Otolaryngol Head & Neck Surg, São Paulo, BrazilUniv Ghent, Ghent Univ Hosp, Dept Otorhinolaryngol, Upper Airway Res Lab, B-9000 Ghent, BelgiumUniversidade Federal de São Paulo, Dept Pathol, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Otolaryngol Head & Neck Surg, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Pathol, São Paulo, BrazilWeb of Scienc

Convergence of two major pathophysiologic mechanisms in nasal polyposis : immune response to Staphylococcus aureus and airway remodeling

This review is addressed two pathophysiologic mechanisms implicated in the pathogenesis of nasal polyposis: the unique remodeling process found in nasal polyp tissue and the immune response of patients with nasal polyposis to Staphylococcus aureus. These two theories converge to the same direction in different aspects, including decreased extracellular matrix production, impaired T regulation and favoring of a Th2 immune response. In patients with nasal polyposis, an exaggerated immune response to Staphylococcus aureus may aggravate the airway remodeling process

Convergence of two major pathophysiologic mechanisms in nasal polyposis: immune response to Staphylococcus aureus and airway remodeling

This review is addressed two pathophysiologic mechanisms implicated in the pathogenesis of nasal polyposis: the unique remodeling process found in nasal polyp tissue and the immune response of patients with nasal polyposis to Staphylococcus aureus.\ud \ud These two theories converge to the same direction in different aspects, including decreased extracellular matrix production, impaired T regulation and favoring of a Th2 immune response.\ud \ud In patients with nasal polyposis, an exaggerated immune response to Staphylococcus aureus may aggravate the airway remodeling process

Nasal polyposis : more than a chronic inflammatory disorder : a disease of mechanical dysfunction : the São Paulo position

Introduction The importance of our study lies in the fact that we have demonstrated the occurrence of mechanical dysfunction within polypoid tissues, which promotes the development of polyps in the nasal cavity. Objective To change the paradigm of nasal polyposis (NP). In this new conception, the chronic nasal inflammatory process that occurs in response to allergies, to pollution, to changes in the epithelial barrier, or to other factors is merely the trigger of the development of the disease in individuals with a genetic predisposition to an abnormal tissue remodeling process, which leads to a derangement of the mechanical properties of the nasal mucosa and, consequently, allows it to grow unchecked. Data Synthesis We propose a fundamentally new approach to intervening in the pathological process of NP, addressing biomechanical properties, fluid dynamics, and the concept of surface tension. Conclusion The incorporation of biomechanical knowledge into our understanding of NP provides a new perspective to help elucidate the physiology and the pathology of nasal polyps, and new avenues for the treatment and cure of NP

Orbital decompression in exophthalmos by combined external and endonasal endoscopic approach

A reducao da proptose na oftalmopatia por doenca Graves pode ser obtida atraves de varias tecnicas. A descompressao endonasal auxiliada por endoscopio pode ser utilizada isoladamente ou combinada com outras tecnicas. Com o objetivo de avaliar o efeito da descompressao orbital por via externa e endoscopica endonasal, 15 pacientes portadores de proptose por doenca de Basedow-Graves foram submetidos a 17 descompressoes orbitais. Por acesso cutaneo foram removidas a parede ossea lateral e a porcao medial ao canal infra-orbital da parede inferior da orbita e por acesso endonasal auxiliado por endoscopio foi removida a parede medial da orbita. No periodo que variou de seis a 18 meses de acompanhamento pos-operatorio foi observada uma reducao media da proptose de 6,00 mm, um paciente apresentou diplopia pos-operatoria (6 por cento) e nao houve piora na acuidade visual. Concluindo, a tecnica de descompressao orbital por via externa e endonasal auxiliada por endoscopia mostrou-se segura e eficaz na reducao da proptose e com baixa morbidadeBV UNIFESP: Teses e dissertaçõe

LTD4 and TGF-β1 Induce the Expression of Metalloproteinase-1 in Chronic Rhinosinusitis via a Cysteinyl Leukotriene Receptor 1-Related Mechanism

Background: Cysteinyl leukotrienes (CysLTs) play a crucial role in the pathogenesis of airway remodeling. The use of CysLTs receptor antagonists has been included in the management of asthma and rhinitis. However, despite the action of these compounds on leukotriene production has been well documented, their role in airway remodeling remains unclear. Objective: We aimed to investigate the capability of the leukotriene receptor antagonist Montelukast to inhibit MMPs release after CysLTs stimulation in nasal tissue fibroblasts. Methods: Fibroblasts were isolated from sinunasal tissue collected from five patients suffering of chronic rhinosinusitis without nasal polyposis. Cells were cultured and stimulated first with LTC4 and LTD4 (10−10, 10−8, 10−6 M) using as pre-stimulus 10 ng/mL of: IL-4, IL-13, or TGF-beta1 and in presence or absence of Montelukast (10−10, 10−8, 10−6 M). To evaluate the regulation of MMP-1 and TIMP-1 we used enzyme immunoassays and to evaluate CysLT1 receptor we used real time PCR. Results: LTD4 but not LTC4 induced production of mRNA for CysLT1 receptor in a dose dependent manner and with an additive effect when the cells where primed with TGF-β1. TNF-α, IL-4, and IL-13 did not influence the expression of the receptor. Levels of MMP-1 but not of TIMP-1 were statistically enhanced in cells primed with TGF-β1 and stimulated with LTD4. Montelukast significantly decreased Cys-LT1 receptor and MMP-1 concentrations in a dose-dependent way in cells stimulated with LTD4 and TGF-β1 separately and when they were applied together. Conclusion: The leukotriene pathway may play an important role in extra-cellular matrix formation in an inflamed environment, such as chronic sinusitis and, consequently, leukotriene receptor antagonists such as Montelukast may be of great benefit in management of this disease

Dendritic cell subset expression in severe chronic rhinosinusitis with nasal polyps

Purpose of review Two main pillars are implicated in nasal polyposis development: a severe imbalance in immunomodulation and a mechanical dysfunction because of an abnormal remodeling process. Dendritic cells play a crucial role in the link between innate and adaptive immune response and orchestrating the T-cell response and are implicated in the severe inflammatory process found in nasal polypoid tissue. This review summarizes the existent knowledge about dendritic cells in nasal polyposis. Recent findings Dendritic cells are found increased in nasal polyposis, regardless of subset. Of interest, plasmacytoid dendritic cells are decreased in patients with a more severe Th2 profile, suggesting an important role of the cytokines milieu in their functional response or that plasmacytoid dendritic cell could act mitigating the inflamed process found in polypoid tissue. Summary Understanding the dendritic cell subset expression in different environments, as well as the effect of these subsets on T-cell differentiation will greatly improve the development of new therapies in nasal polyposis.Univ Antwerp, Dept Biomed Sci, Lab Proteinchem, Prote Epigenet Signaling, Antwerp, BelgiumUniv Fed Sao Paulo, ENT Res Lab, Dept Otolaryngol Head & Neck Surg, Rua Otonis,700 Piso Super,Vila Clementino, BR-04025002 Sao Paulo, SP, BrazilUniv Fed Sao Paulo, ENT Res Lab, Dept Otolaryngol Head & Neck Surg, Rua Otonis,700 Piso Super,Vila Clementino, BR-04025002 Sao Paulo, SP, BrazilWeb of Scienc