Proteomic analysis of mucus from chronic rhinosinusitis patients with or without nasal polyps
Ontology highlight
ABSTRACT:
INSTRUMENT(S): LTQ
ORGANISM(S): Homo Sapiens (ncbitaxon:9606)
SUBMITTER: Dr Richard R. Drake
PROVIDER: MSV000079984 | MassIVE | Fri Jul 22 15:53:00 BST 2016
SECONDARY ACCESSION(S): PXD004144
REPOSITORIES: MassIVE
Similar Datasets
Project description:Patients with chronic rhinosinusitis (CRS) have abnormal immune responses triggered by a variety of infectious agents, airborne toxins and fungi. Respiratory epithelial cells serve as relay stations capable of amplifying or augmenting cues received from external stimuli to nearby immune cells located in the sinus mucosa. Previous studies have identified increases in complement components and complement gene expression in the mucosa of patients with atopic CRS with nasal polyps (CRSwNP). As part of a larger study, we used shotgun proteomics to quantify changes in mucus proteins between patients with and without nasal polyps.
2016-05-26 | PXD004144 | Pride
Project description:Mucus is a protein-based gel secreted by specialized epithelial cells that protects the gastrointestinal mucosa from microorganism attack and irritating agents. Experiments in mice have demonstrated that when the mucosa is infected or inflamed, the mucus becomes enriched with broad-spectrum bactericidal compounds known as antimicrobial peptides (AMPs). Although AMP gene expression has been identified in both immune and epithelial cells, how inflammation regulates AMP secretion in the mucus remains unclear, and the efficacy of AMP-enriched mucus in defending against microorganisms has not been assessed. We have developed a “mucosoid” culture model that simulates the healthy human stomach epithelium. In these cultures, epithelial cells form a barrier and can differentiate into mucus-secreting cells. The accumulation of mucus on the apical side facilitates the detection of AMPs and the assessment of their bactericidal properties. We report that cytokines TNFa, IL1b and IFNg enhance the secretion of the AMPs lactotransferrin, lipocalin2, C3A, and CXCL9 into the mucus. The mucus from inflamed cells which contains the aforementioned AMPs partially kills Helicobacter pylori, the sole stomach pathogen. However, H. pylori can inhibit this defence by reducing AMP gene expression in inflamed epithelial cells. These results reveal that secreted mucus is a relevant effector of epithelial immunity but pathogens like H. pylori can subvert these defences to persist in the mucosa.
2024-09-09 | GSE268591 | GEO
Project description:Our data demonstrates an increased number of submucosal glands in the sinus mucosa of pediatric patients with chronic rhinosinusitis (CRS). Additionally, data in the literature indicates differentially altered expression of innate markers of immunity and of inflammatory mediators in the sinus mucosa of adult patients with cystic fibrosis, non-CF controls, and controls. Keywords: Differciation Study
2008-02-08 | GSE10406 | GEO
Project description:By incompletely understood mechanisms, type 2 (T2) inflammation present in the airways of severe asthmatics drives the formation of pathologic mucus which leads to airway mucus plugging. Here we investigate the molecular role and clinical significance of intelectin-1 (ITLN-1) in the development of pathologic airway mucus in asthma. Through analyses of human airway epithelial cells we find that ITLN1 gene expression is highly induced by interleukin-13 (IL-13) in a subset of metaplastic MUC5AC+ mucus secretory cells, and that ITLN-1 protein is a secreted component of IL-13-induced mucus. Additionally, we find ITLN-1 protein binds the C-terminus of the MUC5AC mucin and that its deletion in airway epithelial cells partially reverses IL-13-induced mucostasis. Through analysis of nasal airway epithelial brushings, we find that ITLN1 is highly expressed in T2-high asthmatics, when compared to T2-low children. Furthermore, we demonstrate that ITLN1 gene expression is significantly reduced and ITLN-1 protein expression is lost through a common genetic variant that is associated with protection from the formation of mucus plugs in T2-high asthma. This work identifies one of the first biomarkers and targetable pathways for the treatment of mucus obstruction in asthma.
2024-04-04 | GSE254127 | GEO
Project description:Objective: Reg3g has been proposed to have a protective role against infection due to its bactericidal effect on Gram-positive bacteria, but evidence from in vivo studies is lacking. Therefore we generated a Reg3g-/- mouse, to determine its role in intestinal homeostasis and protection against experimental infection. Methods: Reg3g-/- mice were phenotyped using histological methods and a range of innate and immune markers. To investigate the antimicrobial role of Reg3g we experimentally infected mice with Gram-positive Listeria monocytogenes and Gram-negative Salmonella entertitidis and measured translocated bacteria, mucosal and systemic markers of infection. Results: Reg3g-/- mice display altered ileal mucus distribution and increased bacterial contact with the epithelium. , concomitant with This increased the inflammatory status in of the ileal mucosa and increased expression of Il-22, myeloperoxidase (MPO) and serum chemokines in serum. In response to infection, Reg3g-/- mice showed transcriptome changes and elevated levels of mucosal MPO in the ileum, but no increased bacterial translocation to the organs. Conclusions: Reg3g is equally distributed throughout the mucus of wild type (wt) mice and its absence results in an altered distribution of the ileal mucus. Reg3g deficiency also results resulted in increased bacterial contact with the epithelium and heightened inflammatory responses in the ileal mucosa. We propose that Reg3g binds pathogens suggesting it and contributes to mucus barrier function by ensnaring bacteria. Compared to wt mice, Reg3g-/- mice infected with S. enteritidis and L. monocytogenes show an increase of mucosal inflammatory markers indicating the protective, anti-microbial roles of Reg3g in defence against both Gram-positive and -negative bacteria. This study was set up according to a one-treatment, one-control design; treatments were inoculation with either Listeria monocytogenes or Salmonella enteritidis bacterial pathogens. The study results contain transcriptional profiles from infected and sham-infected control C57Bl/6 mice. In total, this study includes data from 2 treatments and 1 control of (pooled) wild-type C57Bl/6 mice and Reg3g-/- KO mutant C57Bl/6 mice = 6 arrays.
2014-06-06 | E-GEOD-44409 | biostudies-arrayexpress
Project description:Objective: Reg3g has been proposed to have a protective role against infection due to its bactericidal effect on Gram-positive bacteria, but evidence from in vivo studies is lacking. Therefore we generated a Reg3g-/- mouse, to determine its role in intestinal homeostasis and protection against experimental infection. Methods: Reg3g-/- mice were phenotyped using histological methods and a range of innate and immune markers. To investigate the antimicrobial role of Reg3g we experimentally infected mice with Gram-positive Listeria monocytogenes and Gram-negative Salmonella entertitidis and measured translocated bacteria, mucosal and systemic markers of infection. Results: Reg3g-/- mice display altered ileal mucus distribution and increased bacterial contact with the epithelium. , concomitant with This increased the inflammatory status in of the ileal mucosa and increased expression of Il-22, myeloperoxidase (MPO) and serum chemokines in serum. In response to infection, Reg3g-/- mice showed transcriptome changes and elevated levels of mucosal MPO in the ileum, but no increased bacterial translocation to the organs. Conclusions: Reg3g is equally distributed throughout the mucus of wild type (wt) mice and its absence results in an altered distribution of the ileal mucus. Reg3g deficiency also results resulted in increased bacterial contact with the epithelium and heightened inflammatory responses in the ileal mucosa. We propose that Reg3g binds pathogens suggesting it and contributes to mucus barrier function by ensnaring bacteria. Compared to wt mice, Reg3g-/- mice infected with S. enteritidis and L. monocytogenes show an increase of mucosal inflammatory markers indicating the protective, anti-microbial roles of Reg3g in defence against both Gram-positive and -negative bacteria.
2014-06-06 | GSE44409 | GEO
Project description:The colon contains a dense metabolically potent microbiota. The colonic O-glycan-rich mucus has been recognized as a key barrier to prevent microbial intrusion, but how this system forms and functions remains unclear. Here, we discovered that the colon mucus is mainly forged by microbiota-dependent secretion of O-glycosylated Muc2 by goblet cells in the ascending colon, where it seamlessly encapsulates the fecal materials including the microbiota. Deletion of O-glycans in the ascending colon impaired the segregating function of the mucous coating, leading to altered structure and metabolic output of the microbiota, and transcriptional homeostasis of the entire host mucosa. These findings represent a paradigm change of the prevailing model of the colon mucus system and provides new insights into host and microbiota symbiosis.
2020-10-28 | GSE133174 | GEO
Project description:The MUCUS clinical trial (https://clinicaltrials.gov: NCT01433471) was established to investigate the effect of Trichuris suis ova on ulcerative colitis patients.
2017-11-11 | GSE96698 | GEO
Project description:<p><strong>PURPOSE:</strong> Olfactory dysfunction (OD) is a debilitating symptom frequently reported by patients with chronic rhinosinusitis (CRS) and it is associated with a dysregulated sinonasal inflammation. However, little information is available about the effect of the inflammation-related nasal microbiota and related metabolites on the olfactory function in these patients. Therefore, the current study aimed to investigate the nasal microbiota-metabolites-immune interactions and their role in the pathogenesis of OD in CRS patients.</p><p><strong>METHODS:</strong> 23 and 19 CRS patients with and without OD (NOD), respectively, were enrolled in the present study. The 'Sniffin' Sticks' was used to measure the olfactory function, while the metagenomic shotgun sequencing and the untargeted metabolomic profiling were performed to assess the differences in terms of the nasal microbiome and metabolome between the two groups. The levels of nasal mucus inflammatory mediators were investigated by a multiplex flow Cytometric Bead Array (CBA).</p><p><strong>RESULTS:</strong> A decreased diversity in the nasal microbiome from the OD group compared to the NOD group was evidenced. The metagenomic analysis revealed a significant enrichment of <em>Acinetobacter johnsonii</em> in the OD group, while <em>Mycoplasma arginini</em>, <em>Aeromonas dhakensis</em> and <em>Salmonella enterica</em> were significantly less represented (LDA value > 3, p < 0.05). The nasal metabolome profiles were significantly different between the OD and NOD groups (P < 0.05). The purine metabolism was the most significantly enriched metabolic subpathway in OD patients compared with NOD patients (P < 0.001). The expressions of IL-5, IL-8, MIP-1alpha, MCP-1 and TNF were statistically and significantly increased in the OD group (P < 0.05). All these data, including the dysregulation of the nasal microbiota, differential metabolites and elevated inflammatory mediators in OD patients demonstrated a clear interaction relationship.</p><p><strong>CONCLUSIONS:</strong> The disturbed nasal microbiota-metabolite-immune interaction networks may be implicated in the pathogenesis of OD in CRS patients and the underlying pathophysiological mechanisms need to be further investigated in future studies.</p>
2023-05-12 | MTBLS7584 | MetaboLights
Project description:The colon contains a dense metabolically potent microbiota. The colonic O-glycan-rich mucus has been recognized as a key barrier to prevent microbial intrusion, but how this system forms and functions remains unclear. Here, we discovered that the colon mucus is mainly forged by microbiota-dependent secretion of O-glycosylated Muc2 by goblet cells in the ascending colon, where it seamlessly encapsulates the fecal materials including the microbiota. Deletion of O-glycans in the ascending colon impaired the segregating function of the mucous coating, leading to altered structure and metabolic output of the microbiota, and transcriptional homeostasis of the entire host mucosa. These findings represent a paradigm change of the prevailing model of the colon mucus system and provides new insights into host and microbiota symbiosis.
2020-10-28 | GSE133256 | GEO