Role of the Aryl Hydrocarbon Receptor in the Pathogenesis of Chronic Rhinosinusitis with Nasal Polyps

Inflammation ◽  
2013 ◽  
Vol 37 (2) ◽  
pp. 387-395 ◽  
Author(s):  
Ping Wei ◽  
Guo-hua Hu ◽  
Hou-yong Kang ◽  
Hong-bing Yao ◽  
Wei Kou ◽  
...  
2018 ◽  
Vol 141 (2) ◽  
pp. 586-600.e6 ◽  
Author(s):  
Heng Wang ◽  
Danh C. Do ◽  
Jinxin Liu ◽  
Baofeng Wang ◽  
Jingjing Qu ◽  
...  

2021 ◽  
Vol 19 ◽  
pp. 205873922110656
Author(s):  
Aigerim Kvarantan ◽  
Vedran Balta ◽  
Neven Zarkovic ◽  
Tea Horvat ◽  
Tea Vukovic ◽  
...  

Objective Сhronic rhinosinusitis with nasal polyps (CRSwNPs) is a distinct entity within the chronic rhinosinusitis group of diseases, which are chronic upper airway diseases with several pheno- and endotypes. Oxidative stress plays an important role in the pathogenesis of CRSwNPs. The aim was to assess the association between expression of the aryl hydrocarbon receptor (AhR) and 4-hydroxynonenal (4-HNE) in patients with CRSwNPs. Methods The study included 26 patients who underwent endoscopic sinus surgery: Fourteen patients with CRSwNPs, and 12 controls with healthy sinus mucosa. Expression of AhR and 4-HNE was assessed in tissue samples using immunohistochemistry. The level of 4-HNE in serum samples was measured using the ELISA assay. Total oxidative capacity (TOC) was assessed by measuring the peroxidase activity. Results Higher levels of 4-HNE expression were observed in tissues (3, range 1–3 vs. 0, range 0–0 p<0.001) and serum (27.7±11.5 vs 9.8±7.7 pmol/mg, p < 0.001) samples of CRSwNPs patients, as compared to healthy controls. Higher expression of AhR was found in inflammatory cells (plasma cells, lymphocytes, eosinopholes) of CRSwNPs patients, compared to controls (3, range 1–3 vs. 2, range 1–2, p = 0.001). There were no differences in TOC across groups (0.0285±0.0207 vs 0.02, 978±0.0197 µM H2O2 eq., p = 0.848). Patients with bronchial asthma (57%) had abundant eosinophil in tissue samples. Patients with recalcitrant CRSwNPs had higher 4-HNE serum levels, compared to non-recalcitrant cases (27.3 vs 24.2 pmol/mg, p = 0.339). Conclusion Patients suffering from CRSwNPs have oxidative stress–mediated overexpression of AhR, which is linked to a chronic inflammatory response in the paranasal sinus tissues.


2021 ◽  
pp. 2100539
Author(s):  
Robert S. Chapkin ◽  
Laurie A. Davidson ◽  
Hyejin Park ◽  
Un‐Ho Jin ◽  
Yang‐Yi Fan ◽  
...  

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Jianwei Zhang ◽  
Lei Han ◽  
Feng Chen

Abstract Background Let-7a-5p is demonstrated to be a tumor inhibitor in nasopharyngeal carcinoma. However, the role of let-7a-5p in chronic rhinosinusitis with nasal polyps (CRSwNP) has not been reported. This study is designed to determine the pattern of expression and role of let-7a-5p in CRSwNP. Methods The expression level of let-7a-5p, TNF-α, IL-1β, and IL-6 in CRSwNP tissues and cells were detected by RT-qPCR. Western blot assay was carried out to measure the protein expression of the Ras-MAPK pathway. Dual luciferase reporter assay and RNA pull-down assay were used to explore the relationship between let-7a-5p and IL-6. Results Let-7a-5p was significantly downregulated in CRSwNP tissues and cells. Moreover, the mRNA expression of TNF-α, IL-1β and IL-6 was increased in CRSwNP tissues, while let-7a-5p mimic inhibited the expression of TNF-α, IL-1β and IL-6. Besides that, let-7a-5p was negatively correlated with TNF-α, IL-1β and IL-6 in CRSwNP tissues. In our study, IL-6 was found to be a target gene of let-7a-5p. Additionally, let-7-5p mimic obviously reduced the protein levels of Ras, p-Raf1, p-MEK1 and p-ERK1/2, while IL-6 overexpression destroyed the inhibitory effect of let-7a-5p on the Ras-MAPK pathway in CRSwNP. Conclusion We demonstrated that let-7a-5p/IL-6 interaction regulated the inflammatory response through the Ras-MAPK pathway in CRSwNP.


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