Increased lipopolysaccharide content is positively correlated with glucocorticoid receptor‐beta expression in chronic rhinosinusitis with nasal polyps

Abstract

Introduction Chronic rhinosinusitis with nasal polyps (CRSwNP) is a common and frequently occurring disease of the upper respiratory tract. The nasal instillation of the Gram‐negative (G−) bacterial product lipopolysaccharide (LPS) can induce not only acute sinusitis but also the development of CRSwNP in animal models. Nevertheless, the expression and distribution of LPS in patients with CRSwNP have not been investigated. And the study was to investigate the expression of LPS and its relationship with glucocorticoid receptors (GRs) in CRSwNP. Methods Multiple methods, including bacterial culture and immunohistochemistry, were used to detect and analyze nasal bacteria, plasma LPS content, and the levels of LPS and GR‐α/β, cluster of differentiation 68 (CD68), and myeloperoxidase (MPO) expression, as well as their relationship in CRSwNP. Results The number of G− bacteria and Escherichia coli (E. coli) was not significantly different between CRSwNP subjects and the controls. However, the positive rate of LPS was much higher than that of E. coli in CRSwNP subjects and was significantly higher in noneosinophilic CRSwNP subjects than in eosinophilic CRSwNP subjects. Moreover, the LPS levels were positively correlated with GR‐β but not GR‐α expression in CRSwNP. Immunofluorescence assays showed that LPS was mainly detected in CD68+ macrophages and MPO+ neutrophils, in addition to histiocytes, in CRSwNP. Conclusions Persistent LPS in CRSwNP can lead to unresolved mucosal inflammation, eventually leading to tissue remodeling and the development of CRSwNP. Our findings suggest that increased LPS content and possible resistance to glucocorticoids may be one of the important pathogenic mechanisms of G− bacteria in CRSwNP.

The Expression and Regulation of Na⁺-K⁺-ATPase in Nasal Epithelial Cells of Chronic Rhinosinusitis with Nasal Polyps

“…In HNECs culture and stimulation experiment, NKA mRNA levels and NKA activities were significantly suppressed by SEB, LPS, IFN-γ, IL-4, IL-13, and IL-1β. These findings were partially in line with previous reports indicating that NKA expression or activity could be suppressed by SEB, LPS, IFN-γ, IL-1β, or TNF-α intervention on a variety of tissues and cells including rat intestinal mucosa [26], rat astrocytes [27], human intestinal xenografts [28], rat cardiac myocytes [29], and HepG2 cells (a human liver cancer cell line) [30], et al Previous studies have indicated the SEB and LPS could exacerbate inflammatory responses of HNECs in CRSwNP [31][32][33], thus, collectively, it can be surmised that NKA function in HNECs is impaired following SEB and LPS treatment, indicating that bacterial infection could trigger aggravation of inflammation via impairing NKA function in HNECs. In addition, type 1 IFN-γ, type 2 IFNs (IL-4 and IL-13), and IL-1β could also exert important roles in the inflammatory responses in CRSwNP [4,34,35]; therefore, it is reasonable to speculate that NKA function in HNECs is also impaired following type 1 IFN-γ, type 2 IFNs (IL-4 and IL-13), and IL-1β stimulation, indicating that these IFNs could also induce trigger inflammatory responses via impairing NKA function in HNECs.…”

Identification of a circRNA/miRNA/mRNA ceRNA Network as a Cell Cycle-Related Regulator for Chronic Sinusitis with Nasal Polyps

“…CRSwNP is heterogeneous disease that is associated with significant public health problems and causes heavy socioeconomic burden. 28 , 29 Abnormal gene expression is a key factor leading to the high incidence of CRSwNP, 30 , 31 but it is unclear how these genes are regulated. In our study, we explored the function of a circRNA/miRNA/mRNA ceRNA network in regulating CRSwNP through bioinformatics analysis and RT-qPCR verification.…”

Plasma Exosomes Transfer miR-885-3p Targeting the AKT/NFκB Signaling Pathway to Improve the Sensitivity of Intravenous Glucocorticoid Therapy Against Graves Ophthalmopathy

“…Go enrichment analysis results showed that differential exosome miRNA target genes were significantly enriched in cytokine receptor activity and response to lipopolysaccharide, which were closely related to the mechanism of glucocorticoids (32)(33)(34)(35)(36). Studies have found that increased stress of lipopolysaccharide can lead to GR exon variation (35), and the increase in ITS content is positively correlated with the expression of GR-b (36). GR itself acts as a cytokine receptor, and its ability to respond to glucocorticoids is closely related to cytokine receptor activity.…”

“…Based on the above evidence, 35 differential exosome miRNA target genes enriched by KEGG into the chemokine signaling pathway were selected for follow-up analysis in this study. Go enrichment analysis results showed that differential exosome miRNA target genes were significantly enriched in cytokine receptor activity and response to lipopolysaccharide, which were closely related to the mechanism of glucocorticoids ( 32 – 36 ). Studies have found that increased stress of lipopolysaccharide can lead to GR exon variation ( 35 ), and the increase in ITS content is positively correlated with the expression of GR-β ( 36 ).…”