Septum submucosal glands exhibit aberrant morphology and reduced mucin production in chronic rhinosinusitis

Introduction. Antimicrobial peptides and proteins (AMPs) constitute the first line of defense against pathogenic microorganisms in the airway. The association between AMPs and chronic rhinosinusitis with nasal polyps (CRSwNP) requires further investigations. This study is aimed at investigating the expression and regulation of major dysregulated AMPs in the nasal mucosa of CRSwNP. Methods. The expression of AMPs was analyzed in nasal tissue from patients with eosinophilic (E) CRSwNP and nonECRSwNP and healthy subjects using RNA sequencing. The 10 most abundant AMPs expressed differentially in CRSwNP patients were verified by real-time PCR, and of these, the expression and regulation of secretory leukoprotease inhibitor (SLPI) and clusterin (CLU) were investigated further. Results. The 10 most abundant AMPs expressed differentially in CRSwNP compared to healthy control, regardless of subtypes, included BPIFA1, BPIFB1, BPIFB2, CLU, LTF, LYZ, and SLPI, which were downregulated, and S100A8, S100A9, and HIST1H2BC, which were upregulated. ELISA and immunofluorescence confirmed the decreased expression of SLPI and CLU levels in CRSwNP. SLPI is expressed in both nasal epithelial cells and glandular cells, whereas CLU is mainly expressed in glandular cells. AB/PAS staining further demonstrated that both SLPI and CLU were mainly produced by mucous cells in submucosal glands. Furthermore, the numbers of submucosal glands were significantly decreased in nasal polyp tissue of CRSwNP compared to nasal tissue of controls. SLPI was downregulated by TGF-β1 and IL-4 in cultured nasal tissues in vitro, while CLU expression was inhibited by TGF-β1. Glucocorticoid treatment for 2 weeks significantly increased the expression of all downregulated AMPs, but not LYZ. Additionally, budesonide significantly increased the expression of SLPI and CLU in cultured nasal tissues. Conclusion. The expression of major antimicrobial proteins is significantly decreased in nasal tissue of CRSwNP. The expression of SLPI and CLU is correlated with the numbers of submucosal glands and regulated by inflammatory cytokines and glucocorticoids.

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Secretion Rates of Human Nasal Submucosal Glands from Patients with Chronic Rhinosinusitis or Cystic Fibrosis

American Journal of Rhinology and Allergy ◽

10.2500/ajra.2015.29.4213 ◽

2015 ◽

Vol 29 (5) ◽

pp. 334-338 ◽

Cited By ~ 5

Author(s):

Jin Hyeok Jeong ◽

Peter H. Hwang ◽

Do-Yeon Cho ◽

Nam Soo Joo ◽

Jeffrey J. Wine

Keyword(s):

Cystic Fibrosis ◽

Chronic Rhinosinusitis ◽

Submucosal Glands ◽

Secretion Rates

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Human Cathelicidin Antimicrobial Peptide is Up-Regulated in the Eosinophilic Mucus Subgroup of Chronic Rhinosinusitis Patients

American Journal of Rhinology ◽

10.2500/ajr.2007.21.3048 ◽

2007 ◽

Vol 21 (4) ◽

pp. 395-401 ◽

Cited By ~ 17

Author(s):

Eng Hooi Ooi ◽

Peter-John Wormald ◽

A. Simon Carney ◽

Craig Lloyd James ◽

Lor Wai Tan

Keyword(s):

Antimicrobial Peptide ◽

Chronic Rhinosinusitis ◽

Nasal Mucosa ◽

Innate Defense ◽

Protein Levels ◽

Submucosal Glands ◽

Tissue Homogenates ◽

Mrna And Protein Expression ◽

Polymerase Chain ◽

And Control

Background Eosinophilic mucus chronic rhinosinusitis (EMCRS) patients are a subgroup of CRS with a poorer prognosis due to frequent recurrences of disease. The cathelicidin antimicrobial peptide (CAMP) is an important innate defense peptide but its role in CRS is not well characterized. The purpose of this study was to investigate CAMP mRNA and protein expression from EMCRS, CRS, and normal control patients. Methods Biopsy specimens of nasal mucosa and nasal polyps were taken from 59 CRS patients and 9 controls. CAMP mRNA and protein levels were analyzed by real-time quantitative reverse-transcriptase polymerase chain reaction, immunoassay, Western blot, and immunohistochemistry. Results The expression of CAMP mRNA was significantly increased in EMCRS patients compared with CRS patients (p = 0.0004). By immunohistochemistry, expression of CAMP was localized to nasal epithelial, submucosal glands, and inflammatory subepithelial cells. Western blotting confirmed the presence of CAMP in EMCRS, CRS, and control patients. However, we did not detect statistically significant differences in the protein levels in tissue homogenates between EMCRS, CRS, and control patients. Conclusion This study shows expression of CAMP in nasal mucosa supporting its role in innate defenses against inhaled pathogens. Although CAMP mRNA was up-regulated in EMCRS patients, there were no statistically significant differences in protein levels in the nasal mucosa of EMCRS compared with CRS patients and controls.

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Induction of the endogenous sialoglycan ligand for eosinophil death receptor Siglec-8 in chronic rhinosinusitis with hyperplastic nasal polyposis

Glycobiology ◽

10.1093/glycob/cwab018 ◽

2021 ◽

Author(s):

Hyun Sil Lee ◽

Anabel Gonzalez-Gil ◽

Virginia Drake ◽

T August Li ◽

Ronald L Schnaar ◽

...

Keyword(s):

Chronic Rhinosinusitis ◽

Nasal Polyposis ◽

Middle Turbinate ◽

Death Receptor ◽

Allergic Inflammation ◽

Keratan Sulfate ◽

Airway Disease ◽

Immunoblot Analysis ◽

Submucosal Glands ◽

Disease Quantification

Abstract Siglec-8, an immune-inhibitory sialoglycan binding lectin (S8), is expressed on the surface of eosinophils and mast cells, which are potent mediators of allergic inflammation. When S8 engages endogenous sialoglycan ligands, eosinophils undergo apoptosis and mast cell mediator release is inhibited. In the human airway, Siglec-8 ligands (S8L) are sialylated keratan sulfate chains carried on isoforms of the protein Deleted in Malignant Brain Tumors-1 (DMBT1), an immunoregulatory protein that we recently identified as the endogenous ligand for S8, DMBT1S8. We herein report that S8L is overexpressed in chronic rhinosinusitis with nasal polyposis (CRSwNP), a prevalent eosinophilic laden airway disease. Quantification and comparison of the degree to which DMBT1 carries the S8L by immunoblot analysis and lectin blot overlay, respectively, from nasal lavage showed that the S8L/DMBT1 ratio was significantly increased in CRSwNP vs. control or CRS patients. We identified the histological sites of S8L and DMBT1 expression in fresh surgically resected human nasal polyps. Histochemistry of diseased polyps and adjacent nondiseased middle turbinate (MT) tissue from CRSwNP demonstrated colocalization of S8L and DMBT1 with highest staining in submucosal glands >> epithelium > stoma. S8L expression was specifically elevated in the submucosal glands and epithelium of polyp tissue compared to MT. We hypothesize that expression of the isoform of DMBT1 carrying the Siglec-8 binding sialoglycan, DMBT1S8, is induced in polyps of CRSwNP specifically at the site of disease, is produced in the submucosal glands of polyps and secreted into the lumen of the sinonasal cavity as a host response to mitigate eosinophil-mediated inflammation.

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