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Flow cytometric sinonasal epithelial cell (SNEC) c-Met expression after hepatocyte growth factor (HGF) stimulation. SNECs from control and chronic rhinosinusitis with nasal polyp (CRSwNP) patients were stimulated with 50 ng/mL of HGF and stained with c-Met PE antibody and analyzed by flow cytometry. At baseline both controls and CRSwNP patients express 95-100% of c-Met. The panel on the left shows that controls stimulated with HGF do not modify c-Met expression. CRSwNP SNECs stimulated with HGF is depicted on the right, which shows nearly a 50% reduction of membrane bound c-Met protein.
Source publication
Hepatocyte growth factor (HGF) is a growth factor thought to attenuate Th2-driven eosinophilic airway inflammatory responses. Increased expression of HGF and its receptor c-Met in nasal polyps suggests a role in disease pathogenesis. The effect of HGF on human sinonasal epithelial cell (SNEC) responses to Th2 inflammatory cytokines in chronic rhino...
Contexts in source publication
Context 1
... c-Met mRNA levels between control and CRSwNP patients after HGF stimulation. To examine protein expression, flow cytometry was used to measure c-Met in CRSwNP and control SNECs stimulated with HGF before growth at the ALI. We observed a substantial decrease in membrane bound c-Met in CRSwNP (50%; range, 40-60%) but not in control patients (95%; Figs. 2 and ...
Context 2
... c-Met mRNA levels between control and CRSwNP patients after HGF stimulation. To examine protein expression, flow cytometry was used to measure c-Met in CRSwNP and control SNECs stimulated with HGF before growth at the ALI. We observed a substantial decrease in membrane bound c-Met in CRSwNP (50%; range, 40-60%) but not in control patients (95%; Figs. 2 and ...
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Background
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Objective
We assessed whether levels of sIgD and IgD⁺ B cells are altered in nasal tissu...
Eotaxin-3 (CCL-26), a potent chemokine for eosinophil recruitment and contributing significantly to the pathogenesis of asthma, is secreted by lung epithelial cells in response to T helper 2 cytokines including interleukin 13 (IL-13). Here we showed that vitamin E forms, but not their metabolites, differentially inhibited IL-13-stimulated generatio...
Citations
... This mediator is known to regulate dendritic cell migration, inhibit epithelial apoptosis, and reduce airway eosinophilia in OVA-allergic mice [25] [26]. HGF can also suppress IL-13-induced eotaxin expression in airway epithelial cells [27] [28]. The low level of HGF may therefore facilitate Th2 responses in AR and mixed rhinitis patients. ...
Background
Endotyping chronic rhinitis has proven hardest for the subgroup of non-allergic rhinitis (NAR) patients. While IgE-related inflammation is typical for allergic rhinitis (AR), no markers have been found that can be seen to positively identify NAR. A further complication is that AR and NAR might co-exist in patients with mixed rhinitis. As previous studies have considered only a limited number of inflammatory mediators, we wanted to explore whether a wider panel of mediators could help us refine the endotyping in chronic rhinitis patients.
Objective
To endotype chronic rhinitis, and non-allergic rhinitis in particular, with help of molecular or cellular markers.
Method
In this study we included 23 NAR patients without allergen sensitizations and with persistent rhinitis symptoms, 22 pollen sensitized rhinitis patients with seasonal symptoms, 21 mixed rhinitis patients with pollen-related symptoms and persistent symptoms outside of the pollen season, and 23 healthy controls without any symptoms. Nasal secretions were collected outside of pollen season and differences between the endotypes were assessed for a broad range of inflammatory mediators and growths factors using a multiplex ELISA.
Results
Although we were able to identify two new nasal secretion makers (IL-12 and HGF) that were low in mixed and AR patients versus NAR and healthy controls, the most intriguing outcome is that despite investigating 29 general inflammatory mediators and growth factors no clear profile of non-allergic or mixed rhinitis could be found.
Conclusion
Classical inflammatory markers are not able to differentiate between non-allergic or mixed rhinitis patients and healthy controls.
... Imbalance of this counter-regulation in the epithelium may be responsible for Th2-biased inflammation. Microarray studies have revealed increased levels of the receptor c-met, whose ligand, hepatocyte growth factor, can antagonize the effects of Th2 cytokines on SNEC in vitro [72]. ...
Chronic rhinosinusitis (CRS) is a prevalent health condition characterized by sinonasal mucosal inflammation lasting at least 12 weeks. Heterogeneous in clinical presentation, histopathology, and therapeutic response, CRS represents a spectrum of disease entities with variable pathophysiology. Increased knowledge of cellular and molecular derangements in CRS suggests potential etiologies and targets for therapy. Microbial elements including fungi, staphylococcal enterotoxin, and biofilms have been implicated as inflammatory stimuli, along with airborne irritants and allergens. Defects in innate immunity have gained increased attention as contributors to the chronic inflammatory state. A combination of host susceptibility and environmental exposure is widely believed to underlie CRS, although direct evidence is lacking. Presently, without precise disease definitions and identifiable universal triggers, CRS pathogenesis is broadly described as multifactorial. Current research is beginning to unravel complex and diverse effects of chronic inflammation on sinonasal mucosal homeostasis, but dysfunctional pathways of inflammatory regulation and resolution require further elucidation.
Background
Poor sleep has significant effects on health contributing to increased morbidity and mortality. The direct and indirect costs of sleep dysfunction total well in to the billions of dollars annually in the United States. Chronic rhinosinusitis (CRS) affects up to 16% of the US population and has been linked to poor sleep quality with up to three quarters of patients with CRS reporting poor sleep quality. There is a growing body of literature evaluating the relationship between sleep and CRS. In this review, we organize and present the current knowledge on the associations between sleep and CRS as well as identify areas for further investigation.
Data sources
A structured literature search from 1946 to 2016 was conducted in the English language using OVID MEDLINE database, PubMed, and EMBASE.
Review methods
Abstracts were reviewed for relevance and appropriate studies were included in the narrative review.
Results
Studies were analyzed and discussed as they pertained to the following categories of CRS and sleep: (1) subjective measures of sleep dysfunction, (2) objective measures of sleep dysfunction, and (3) outcomes on sleep quality following treatment of CRS. Articles on the pathophysiology of sleep dysfunction in CRS were separately reviewed.
Conclusions
An evolving body of research demonstrates that quality of sleep is compromised in the majority of patients with CRS. Following treatment of CRS, there is significant improvement in subjective sleep quality, but additional research investigating objective measures following treatment is still needed. Additionally, further investigation is required to better elucidate the underlying pathophysiology of the relationship between sleep dysfunction and CRS.
Level of Evidence
N/A.
Hepatocyte growth factor (HGF), originally identified as a potent mitogen for mature hepatocytes, is now recognized as a humoral mediator in inflammatory and immune responses. Previous studies indicated that HGF negatively regulated allergic airway inflammation. In view of eosinophils playing a role in the pathogenesis of asthma, especially in airway remodeling as a rich source of pro-fibrogenic mediators, the effects of HGF on the different types of eosinophil secretory functions were examined in this study. We found that HGF significantly inhibited IL-5-induced secretion of TGF-β and VEGF from human eosinophils. The inhibitory effect is not associated with TGF-β transcription; rather, it is associated with ultrastructural granule emptying and loss of intracellular TGF-β contents, indicating HGF inhibits the process of piecemeal degranulation. The effect of HGF on extracellular trap cell death (ETosis) that mediates cytolytic degranulation was also investigated; however, immobilized IgG- or phorbol myristate acetate-induced ETosis was only minimally attenuated by HGF. These results reveal the effect of HGF on the distinct pathways of eosinophil secretory functions and also provide novel insights into the role of HGF in the pathogenesis of allergic inflammation.
Sleep disturbance, reduced quality-of-life (QOL), and other components of "sickness behavior" in patients with chronic rhinosinusitis (CRS) are poorly understood. These complex changes in central behavior are due to the effects of immune mediators acting in the brain. We hypothesized that immune mediators that have been associated with CRS are also associated with sickness behavior, somnifacient complaints, and CRS disease specific QOL.
Twenty patients with CRS were prospectively enrolled and completed the Pittsburgh Sleep Quality Index (PSQI), disease-specific QOL, and olfactory instruments. Ethmoid mucosa was obtained and RT-PCR was performed for the cytokines IL-4,-13, and transforming growth factor-beta (TGF-β). Average change in crossover threshold was calculated and differences in gene expression were correlated with sleep quality, CRS specific QOL and disease severity.
Patients with CRS reported overall poor sleep quality and poor CRS specific QOL with significant correlations between them. Increased expression of TGF-β (r=-0.443;p=0.050) and IL-4 (r=-0.548;p=0.012) correlated with sleep dysfunction while IL-13 expression was linearly associated with worse sleep quality (PSQI scores r=-0.417;p=0.075). IL-4 and TGF-β expression was not associated with CRS disease severity or QOL, while significantly higher levels of IL-13 expression correlated with worse CRS disease severity and QOL.
Patients with CRS exhibited behavioral changes commonly referred to as sickness behavior which include poor sleep quality and reduced QOL. The up-regulation of IL-4 and TGF-β may contribute to inflammatory brain-mediated effects on sleep quality, while IL-13 may be a pleiotropic signaling molecule influencing sleep, QOL, and CRS disease severity.
NA/2b.
Patients with chronic rhinosinusitis (CRS) exhibit centrally mediated behavioral changes commonly referred to as "sickness behavior." Sleep alteration is a component of sickness behavior which is estimated to affect up to 70 million patients annually. Patients with CRS have poor sleep quality, and little is known about the underlying etiology and pathophysiology. This narrative review aims to further organize and present the current knowledge associating sleep and CRS.
A literature search was conducted of the OVID MEDLINE database using key search words including: "chronic rhinosinusitis," "sleep," "sleep disorders," and "sleep dysfunction." Additional keywords "nasal obstruction," "nasal polyp," and "fatigue" were identified and used to further delineate relevant articles.
The articles that specifically addressed sleep and CRS were dissected and presented as follows: (1) chronic rhinosinusitis and sleep; (2) chronic rhinosinusitis and fatigue; (3) chronic rhinosinusitis, nasal obstruction, and sleep; and (4) pathophysiology of sleep in chronic rhinosinusitis (cytokines in both sleep and chronic rhinosinusitis and their association to the neuroimmune biology of chronic rhinosinusitis).
Patients with CRS have sleep dysfunction that is associated with their disease severity and overall quality of life. The etiology of sleep dysfunction in CRS is most likely multifactorial. Increasing evidence suggests sleep dysfunction in patients with CRS is partly due to the inflammatory disease process, and sleep physiology in patients with CRS may be actively regulated by the inflammatory component of the disease.
The European Position Paper on Rhinosinusitis and Nasal Polyps 2012 is the update of similar evidence based position papers published in 2005 and 2007.The document contains chapters on definitions and classification, we now also proposed definitions for difficult to treat rhinosinusitis, control of disease and better definitions for rhinosinusitis in children. More emphasis is placed on the diagnosis and treatment of acute rhinosinusitis. Throughout the document the terms chronic rhinosinusitis without nasal polyps and chronic rhinosinusitis with nasal polyps are used to further point out differences in pathophysiology and treatment of these two entities. There are extensive chapters on epidemiology and predisposing factors, inflammatory mechanisms, (differential) diagnosis of facial pain, genetics, cystic fibrosis, aspirin exacerbated respiratory disease, immunodeficiencies, allergic fungal rhinosinusitis and the relationship between upper and lower airways. The chapters on paediatric acute and chronic rhinosinusitis are totally rewritten. Last but not least all available evidence for management of acute rhinosinusitis and chronic rhinosinusitis with or without nasal polyps in adults and children is analyzed and presented and management schemes based on the evidence are proposed.
Chronic rhinosinusitis (CRS) is a common inflammatory condition of the paranasal sinuses and nasal passages. CRS with nasal polyp (CRSwNP) is a subtype of CRS, and the pathogenesis of CRSwNP remains largely unclear.
This article reviews the literature regarding the pathophysiology of CRSwNP.
Evidence suggests that altered innate immunity, adaptive immunity, tissue remodeling, and/or effects of microorganisms may play a role in the development of CRSwNP. Aberrant arachidonic acid metabolism may also contribute to the pathogenesis of CRSwNP in patients with aspirin-exacerbated respiratory disease.
There have been significant advances in the understanding pathophysiology of CRSwNP. Additional research is needed to elucidate these mechanisms and to determine their relative importance in the pathogenesis of CRSwNP.
