Expression Profiling of Inflammatory Mediators in Pediatric Sinus Mucosa

Wu, Xiaofang; Ghimbovschi, Svetlana; Aujla, Pawandeep K.; Rose, Mary C.; Peña, María

doi:10.1001/archoto.2008.505

Cited by 14 publications

(20 citation statements)

References 24 publications

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“…S100A9 is overexpressed in nasal secretory cells from CRS patients with nasal polyps (28), as well as nasal mucus (29) and nasal lavage fluid from CRS patients (19). S100A8 is overexpressed in sinonasal mucosa tissue from patients with CRS with nasal polyps (30,31).…”

Section: Discussionmentioning

confidence: 99%

Proteomic analysis of pediatric sinonasal secretions shows increased MUC5B mucin in CRS

et al. 2014

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Background: Chronic rhinosinusitis (CRS) is characterized by mucous overproduction and submucosal gland hyperplasia. The global protein profile of sinonasal secretions in pediatric CRS has not been studied. We hypothesized that MUC5B, a glandular mucin, would be relatively increased in CRS secretions compared to other mucins. Methods: Secretions were collected at Children's National Health System (Children's National) from CRS patients undergoing sinus surgery and from control patients without CRS undergoing craniofacial procedures. Proteins were extracted, digested to peptides, and analyzed by mass spectometry. Fold change significance was calculated using the QSpec algorithm. Western blot analysis was performed to validate proteomic findings. results: In total, 294 proteins were identified. Although both MUC5B and MUC5AC were identified in a majority of samples, the relative abundance of MUC5B was found to be significantly higher (P < 0.05). Western blot data validated these findings. Other proteins with the highest significant positive-fold change in CRS samples were BP1 fold-containing family A member 1, chitinase-3-like protein 1, plastin-2, serpin 10, and BP1 fold-containing family B member 1. conclusion: Overall, our data demonstrate an increase of MUC5B abundance in the sinus secretions of pediatric patients with CRS.

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Section: Discussionmentioning

confidence: 99%

Proteomic analysis of pediatric sinonasal secretions shows increased MUC5B mucin in CRS

et al. 2014

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“…To gain insights into SMG hyperplasia in the upper respiratory tract, gene expression microarray analyses were performed to identify differences in global and specific gene expressions in the sinus mucosa of control and CRS patients. Our initial study identified and validated specific inflammatory and innate immune mediator genes that are upregulated in CRS and control sinus mucosa (18). Here, we identify glandular gene products differentially expressed in the sinus mucosa of control, CRS, and CRS/CF patients, and we evaluate their cellular localization in SMGs.…”

Section: Clinical Relevancementioning

confidence: 96%

“…Sinus tissue was obtained from patients with CRS who underwent functional endoscopic sinus surgery at Children's National Medical Center (CNMC, Washington, DC) for CRS refractory to medical management. Exclusion criteria for the control population and the criteria for diagnosing CRS were described previously (18). A diagnosis of CRS in the CRS/CF cohort was based on a combination of clinical presentation, endoscopic nasal examinations, and computerized tomography imaging of the paranasal sinuses.…”

Section: Specimens Of Sinus Mucosamentioning

confidence: 99%

“…Mucosa from the paranasal sinuses that typically included maxillary and ethmoid tissues was collected from CRS and control patients, as described previously (18). When clinically appropriate, mucosa from the frontal and sphenoid sinuses was also collected.…”

Section: Specimens Of Sinus Mucosamentioning

confidence: 99%

“…Sample preparation, expression profiling, and microarray analyses of sinus mucosa samples were performed at the Microarray Core of CNMC, as previously described (18). All data were analyzed using Microarray Analysis Software, version 5.0 (MAS 5.0 algorithm; Affymetrix, Fremont, CA), along with dChip and PLIER algorithms.…”

Section: Gene Expression Profiling and Microarray Data Analysesmentioning

confidence: 99%

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Glandular Gene Expression of Sinus Mucosa in Chronic Rhinosinusitis with and without Cystic Fibrosis

Peters-Hall

Ghimbovschi

et al. 2011

Am J Respir Cell Mol Biol

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Secretory cells in submucosal glands (SMGs) secrete antibacterial proteins and mucin glycoproteins into the apical lumen of the respiratory tract, and these are critical for innate immune mucosal integrity. Glandular hyperplasia is manifested in diseases with obstructive respiratory pathologies associated with mucous hypersecretion, and is predominant in the sinus mucosa of patients with chronic rhinosinusitis (CRS), cystic fibrosis (CF), and clinical symptoms of CRS. To gain insights into the molecular basis of SMG hyperplasia in CRS, gene expression microarray analyses were performed to identify the differences in global and specific gene expression in the sinus mucosa of control, CRS, and CRS/CF patients. A marked up-regulation of 11 glandular-associated genes in CRS and CRS/CF sinus mucosa was evident. The RNA and protein expressions of the four most highly up-regulated genes (DSG3, KRT14, PTHLH, and OTX2) were evaluated. An increased expression of DSG3, KRT14, and PTHLH was demonstrated at the mRNA and protein levels in both CRS and CRS/CF sinus mucosa, whereas the increased expression of OTX2 was evident only for CRS/CF sinus mucosa, implicating OTX2 as a CF-specific gene. Immunofluorescence analysis localized DSG3, PTHLH, and OTX2 to serous cells, and KRT14 to myoepithelial cells, in SMGs. Because glandular hyperplasia is a central histologic feature of CRS, the identification of overexpressed glandular genes in the sinus mucosa lays the groundwork for future studies of glandular hyperplasia, and may ultimately lead to the development of novel treatments for mucous hypersecretion in patients with CRS.

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Localization of Inflammatory Mediators in Pediatric Sinus Mucosa

Mimms²,

Lima³

et al. 2012

Arch Otolaryngol Head Neck Surg

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Objectives Microarray analyses of sinus mucosa in pediatric patients with chronic rhinosinusitis (CRS) have recently demonstrated increased messenger RNA expression of the inflammatory chemokines CXCL5 and CXCL13 and of the innate immune mediators β-defensin 1 (DEFB1), serum amyloid A2 (SAA2), and serpin B4. The objectives of this study were to determine whether these gene products were expressed at the protein level in pediatric sinus mucosa and to determine their localization. Design Immunohistochemical analysis was used to identify protein expression and cellular localization of CXCL5, CXCL13, DEFB1, SAA2, and serpin B4. Coimmunofluorescence staining of inflammatory cells was performed to further evaluate expression of CXCL5 and CXCL13. Setting Pediatric tertiary care facility. Patients Fifteen children with CRS who underwent endoscopic sinus surgery and 8 children who underwent craniofacial or neurosurgical procedures for abnormalities other than sinusitis. Main Outcome Measures Protein expression and cellular localization of CXCL5, CXCL13, DEFB1, SAA2, and serpin B4 in pediatric sinus mucosa. Results Ciliated and basal cells in the pseudostratified epithelium stained positively for the 5 mediators examined in both cohorts. Except for serpin B4, goblet cells did not stain for any mediators in either cohort. Glandular cells stained positively for all 5 mediators in both cohorts. Coimmunofluorescence staining of inflammatory cells showed that CXCL13 was expressed in macrophages, T and B cells but not in neutrophils. CXCL5 was detected only in T cells. Conclusions CXCL5, CXCL13, DEFB1, SAA2, and serpin B4 were expressed at the protein level in the sinus mucosa of controls and pediatric patients with CRS and exhibited cell-specific localization. These mediators, not typically associated with pediatric CRS, may be involved in the inflammatory response and mucus hypersecretion seen in pediatric CRS.

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Expression Profiling of Inflammatory Mediators in Pediatric Sinus Mucosa

Cited by 14 publications

References 24 publications

Proteomic analysis of pediatric sinonasal secretions shows increased MUC5B mucin in CRS

Proteomic analysis of pediatric sinonasal secretions shows increased MUC5B mucin in CRS

Glandular Gene Expression of Sinus Mucosa in Chronic Rhinosinusitis with and without Cystic Fibrosis

Localization of Inflammatory Mediators in Pediatric Sinus Mucosa

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