Expression of Oxidative Stress and Inflammation-Related Genes in Nasal Mucosa and Nasal Polyps from Patients with Chronic Rhinosinusitis

Abstract

Chronic rhinosinusitis (CRS) is a prevalent, multifaceted inflammatory condition affecting the nasal cavity and the paranasal sinuses, frequently accompanied by formation of nasal polyps (CRSwNP). This apparently uniform clinical entity is preceded by heterogeneous changes in cellular and molecular patterns, suggesting the presence of multiple CRS endotypes and a diverse etiology. Alterations of the upper airway innate defense mechanisms, including antimicrobial and antioxidant capacity, have been implicated in CRSwNP etiology. The aim of this study was to investigate mRNA expression patterns of antioxidative enzymes, including superoxide dismutase (SOD) and peroxiredoxin-2 (PRDX2), and innate immune system defense players, namely the bactericidal/permeability-increasing fold-containing family A, member 1 (BPIFA1) and PACAP family members, particularly adenylate-cyclase-activating polypeptide receptor 1 (ADCYAP1) in nasal mucosa and nasal polyps from CRSwNP patients. Additional stratification based on age, sex, allergic comorbidity, and disease severity was applied. The results showed that ADCYAP1, BPIFA1, and PRDX2 transcripts are differentially expressed in nasal mucosa and scale with radiologically assessed disease severity in CRSwNP patients. Sinonasal transcriptome is not associated with age, sex, and smoking in CRSwNP. Surgical and postoperative corticosteroid (CS) therapy improves endoscopic appearance of the mucosa, but variably reverses target gene expression patterns in the nasal cavity of CRSwNP patients. Transcriptional cross-correlations analysis revealed an increased level of connectedness among differentially expressed genes under inflammatory conditions and restoration of basic network following CS treatment. Although results of the present study imply a possible engagement of ADCYAP1 and BPIFA1 as biomarkers for CRSwNP, a more profound study taking into account disease severity and CRSwNP endotypes prior to the treatment would provide additional information on their sensitivity.

Transcriptomic Analysis of Genes Associated with Oxidative Stress in Chronic Rhinosinusitis Patients with Nasal Polyps: Identifying Novel Genes Involved in Nasal Polyposis

“…Previous studies generally focused on the relationship between control and CRS nasal tissues with respect to selected oxidative-stress-related genes, such as iNOS, HO-1, SOD, PRDX, and others [ 14 , 15 , 39 , 52 ]. In this study, we systemically analyzed NP tissues using 84 preset oxidative-stress-related genes, targeting and providing a whole analytic picture of up- and downregulated genes that might contribute to the generation of oxidative stress, including lipid peroxidation and protein nitrotyrosination during nasal polyposis.…”

Oxidative Stress and Air Pollution: Its Impact on Chronic Respiratory Diseases

“…Recently, at the molecular level, the expression of oxidative stress-and inflammationrelated genes in nasal polyps from patients with CRSwNP was evaluated. A significantly lower difference in the expression levels of transcription of antioxidant enzymes, including superoxide dismutase (SOD) and peroxiredoxin-2 (PRDX2), was reported, independent of age, sex, and smoking in patients with CRSwNP [12]. These results correspond to reduced SOD capacity with the increase in oxidative stress.…”

Female reproductive functions of the neuropeptide PACAP

“…The source of PACAP in human biological fluids is mainly unknown, but these studies have highlighted the potential use of PACAP as a biomarker in certain diseases, where changes can reflect the presence and/or progression of a disease (127). Among others, PACAP has a potential biomarker value in dilatative cardiomyopathy, cardiac infarct, Parkinson's disease, migraine, polytrauma and chronic rhinosinusitis (127,(137)(138)(139)(140)(141). A most recent study has highlighted the potential use of PACAP, together with calcitonin gene related peptide (CGRP), in differentiating pediatric migraine from non-migraine headaches (142), while another recent study has shown the association between COVID-survival and VIP/PACAP plasma levels (143).…”