Increased Tissue Expression of Lectin-Like Oxidized LDL Receptor-1 (LOX-1) Is Associated with Disease Severity in Chronic Rhinosinusitis with Nasal Polyps

Abstract

Background: The oxidative stress, induced by both environmental and intrinsic stimuli, underlies the onset and persistency of chronic rhinosinusitis (CRS). Scavenger receptors (SRs) are a broad family of transmembrane receptors involved in a dysfunctional host–environment interaction through a reaction with reactive oxygen species (ROS) production. Objective: We hypothesized possible roles of two major SRs in CRS pathology that can translate to clinical phenotypes or histological subtypes: lectin-like oxidized low-density lipoproteins (LDL) receptor-1 (LOX-1) and scavenger receptor class B type 1 (SR-B1). Patients and Methods: We collected ethmoid sinus mucosa specimens and blood samples from patients with CRS with nasal polyps (CRSwNP; n = 31) or CRS without NP (CRSsNP; n = 13) and 19 control subjects. We performed an RT-PCR analysis, ELISA assay, and immunostaining to determine the expressions and distributions of LOX-1 and SR-B1. Results: The CRSwNP group showed a significant increase in LOX-1 mRNA expression compared to the control group. There was no significant difference in SR-B1 mRNA levels among the three groups. The LOX-1 mRNA levels were positively correlated with the sinus computed tomography (CT) scores. Sinus tissue, but not serum samples, showed elevated concentrations of LOX-1 protein in the CRSwNP group versus the control group. The LOX-1 protein distribution was localized in inflammatory cells and vascular endothelial cells. Conclusion: LOX-1 is a major receptor for oxidized low-density lipoprotein produced by oxidative stress. This is the first study to report alterations in LOX-1 expression and production triggered by persistent inflammatory processes in CRSwNP patients. Our findings reveal complex but important roles for SRs that may contribute to the onset of different CRS phenotypes.

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

“…Lipopolysaccharide reduces cystic fibrosis transmembrane conductance regulator (CFTR)-mediated short-circuit current and increases cytoplasmic and mitochondrial reactive oxygen species, resulting in CFTR carbonylation in mammalian respiratory epithelial cells [ 18 ]. Interestingly, lectin-like, oxidized low-density lipoprotein (LDL) receptor-1, a major receptor for oxidized LDL produced by oxidative stress, is associated with disease severity in CRSwNP [ 19 ], and bactericidal antibiotics promote oxidative damage and programmed cell death in sinonasal epithelial cells [ 20 ]. While some special genes have been targeted in research on CRS, a systemic analysis of the transcriptional levels in oxidative-stress-related genes in nasal polyposis remains lacking.…”

The oxidant-antioxidant imbalance was involved in the pathogenesis of chronic rhinosinusitis with nasal polyps

“…Previous studies have shown that nasal epithelial cells, macrophages, neutrophils, eosinophils and basophils are the sites of oxidative stress in CRSwNP ( 13 , 14 , 16 ). In our study, NOS2 and NOX1 were expressed in epithelial and subcutaneous cells, such as NOS2 + macrophages, as determined by immunofluorescence.…”

“…In contrast, there are many antioxidants in cells that can prevent the production of free radicals or eliminate them quickly, including glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), heme oxygenase (HO) and glutathione reductase (GR) ( 10 ). Recently, oxidative stress has been shown to be involved in the development of CRSwNP ( 13 – 15 ). It was reported that patients with nasal polyps show an increase in oxidants and a decrease in antioxidants ( 16 – 18 ).…”

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

“…Lectin-like oxidized LDL receptor-1 (LOX-1) is one member of these transmembrane receptors. In 2020, Nishida and colleagues found a significant increase in the mRNA expression levels of LOX-1 in CRSwNP patients [19].…”