Nuclear Factor κB/MicroRNA-155 Upregulates the Expression Pattern of Cytokines in Regulating the Relapse of Chronic Sinusitis with Nasal Polyps and the Underlying Mechanism of Glucocorticoid

Abstract

The aim of this study was to explore the upregulated nuclear factor kB (NF-kB)/microRNA-155 (miR-155) in regulating inflammatory responses and relapse of chronic rhinosinusitis (CRS) with nasal polyps (NP), which underlies the molecular mechanism of glucocorticoid treatment. Material/Methods: The study recruited 25 patients with eosinophilic (Eos) CRSwNP, 25 patients with Non-Eos CRSwNP, 25 patients with CRS without NP (CRSsNP) and 30 patients with nasal septum deviation (control group). The expression of NF-kB/miR-155 and inflammatory cytokines was detected in epithelial tissue specimens. Additionally, a mouse model of Eos CRSwNP was established, and the mice were treated by NF-kB inhibitor, miR-155 antagomir, or dexamethasone (DEX) to explore the role of NF-kB/miR-155 and the anti-inflammatory effects of glucocorticoid treatment. Results: Results showed that the expression level of NF-kB/miR-155 was significantly elevated in the Eos CRSwNP group, accompanied by the upregulation of cytokines: tumor necrosis factor (TNF)-a, interleukin (IL)-1, IL-4, IL-5 (P<0.05) compared with the control group, the CRSsNP group or the Non-Eos CRSwNP group. The upregulation of NF-kB/miR-155 increased inflammatory mediator cyclooxygenase2 (COX2) while decreasing antiinflammatory mediator Src homology-2 domain-containing inositol 5-phosphatase 1 (SOCS1), which resulted in the aberrant expression pattern of cytokines in the mice model. DEX treatment inhibited the expression of cytokines and decreased the relapse rate of Eos CRSwNP via inhibiting NF-kB/miR-155 (P<0.05). Conclusions: The upregulation of NF-kB/miR-155 was crucial in mediating the aberrant expression of inflammatory cytokines in Eos CRSwNP. This molecular mechanism is a concern with the high relapse rate of Eos CRSwNP. However, glucocorticoid treatment inhibited the relapse of CRSwNP via downregulation of NF-kB/miR-155.

Analysis of competing endogenous RNA (ceRNA) crosstalk in eosinophilic chronic rhinosinusitis with nasal polyps

“…For instance, upregulation of miR‐125b could increase IFN‐β expression in airway epithelial cells via targeting 4E‐BP1, thus hastening eosinophil infiltration 13 . Experimental evidence indicated that miR‐155 overexpression could result in the increase of tumor necrosis factor (TNF)‐alpha, IL‐1, IL‐4, and IL‐5 in the mouse model of eosinophilic CRSwNP 44 . It has been reported that the abnormal miR‐124 expression in CRSwNP could regulate cellular inflammatory response by inhibiting Aryl hydrocarbon receptor (AHR) expression 45 .…”

Current research into A20 mediation of allergic respiratory diseases and its potential usefulness as a therapeutic target

“…Activation of NF-κB signaling is associated with the production of various pro-inflammatory cytokines, including IL-1, IL-33 and thymic stromal lymphopoietin (TSLP), in human nasal epithelial cells ( 40 ). Glucocorticoid treatment, which is considered the first-line treatment of CRS ( 3 ), has been found to hinder the recurrence of CRS by inhibiting NF-κB signaling ( 41 ). Enhanced NF-κB pathway activation and increased IL-6 and IL-8 levels are observed in patients with CRS ( 42 ), implying the involvement of A20 in CRS pathogenesis and development.…”

Epigenetic modifications in chronic rhinosinusitis with and without nasal polyps

“…The mechanism might be that miR-125b induces the production of type I interferon via targeting 4E-binding protein 1 (4E-BP1), an initiator of eukaryotic translation, in airway epithelial cells ( Zhang et al, 2012 ). Reports have shown that miR-155 is also upregulated in CRS ( Xia et al, 2015 ), particularly in ECRSwNP ( Du et al, 2020 ). The mechanism of miR-155 in ECRSwNP may involve the increase of inflammatory mediator cyclooxygenase 2 (COX2) and the decrease of anti-inflammatory mediator Src homology-2 domain-containing inositol 5-phosphatase 1 (SHIP1) ( Du et al, 2020 ).…”

“…Reports have shown that miR-155 is also upregulated in CRS ( Xia et al, 2015 ), particularly in ECRSwNP ( Du et al, 2020 ). The mechanism of miR-155 in ECRSwNP may involve the increase of inflammatory mediator cyclooxygenase 2 (COX2) and the decrease of anti-inflammatory mediator Src homology-2 domain-containing inositol 5-phosphatase 1 (SHIP1) ( Du et al, 2020 ). Furthermore, the mechanism of glucocorticoids in relieving recurrent CRSwNP is also closely related to the downregulation of miR-155 ( Du et al, 2020 ).…”

“…The mechanism of miR-155 in ECRSwNP may involve the increase of inflammatory mediator cyclooxygenase 2 (COX2) and the decrease of anti-inflammatory mediator Src homology-2 domain-containing inositol 5-phosphatase 1 (SHIP1) ( Du et al, 2020 ). Furthermore, the mechanism of glucocorticoids in relieving recurrent CRSwNP is also closely related to the downregulation of miR-155 ( Du et al, 2020 ). miR-19a is upregulated in the peripheral dendritic cells (DCs) of CRSwNP patients and in the HNEpC of CRS patients ( Luo et al, 2017 ; Shin et al, 2020 ).…”