Role of P2X7R in eosinophilic and non‑eosinophilic chronic rhinosinusitis with nasal polyps

by Selleckchem | Oct 30 2023

Chronic rhinosinusitis with nasal polyps (CRSwNP) is an inflammation‑mediated disease of the nasal mucosa. P2X7R has been reported to be a potential biomarker for inflammation. The aim of the present study was to explore the role of P2X7R in CRSwNP, and the interaction between P2X7R and the NLRP3 inflammasome in the development of CRSwNP. Firstly, the expression profiles of P2X7R in nasal mucosa were investigated using western blotting (WB), polymerase chain reaction (PCR) and immunofluorescence (IF) staining. Next, the effect of inflammatory stimulation with lipopolysaccharides (LPS) combined with 2'(3')‑O‑(4‑benzoylbenzoyl) adenosine 5'‑triphosphate triethylammonium salt (BzATP) on primary human nasal epithelial cells (HNECs) was determined. Then, the therapeutic effect of the selective P2X7R antagonist, A740003, on P3X7R, NOD‑like receptor pyrin domain containing 3 (NLRP3) inflammasome and IL‑1β alterations in HNECs was explored using enzyme‑linked immunosorbent assay, WB and PCR. It was found that P2X7R was overexpressed in CRSwNP, especially in eosinophilic CRSwNP, the expression of P2X7R, NLRP3 and IL‑1β were upregulated in HNECs after induction by LPS combined with BzATP; but the expression of NLRP3 and IL‑1β were downregulated after stimulation with A740003. The aforementioned results indicate that P2X7R‑mediated NLRP3 inflammasome activation may have a role in the pathogenesis of CRSwNP.

Comments:

The study aimed to investigate the role of P2X7R (a receptor involved in inflammation) in chronic rhinosinusitis with nasal polyps (CRSwNP), as well as its interaction with the NLRP3 inflammasome, which is implicated in the development of CRSwNP.

To begin with, the researchers examined the expression profiles of P2X7R in the nasal mucosa using various techniques such as western blotting, polymerase chain reaction (PCR), and immunofluorescence staining. They found that P2X7R was overexpressed in CRSwNP, particularly in eosinophilic CRSwNP.

In order to determine the effect of inflammatory stimulation on primary human nasal epithelial cells (HNECs), the researchers exposed the cells to lipopolysaccharides (LPS) combined with 2'(3')‑O‑(4‑benzoylbenzoyl) adenosine 5'‑triphosphate triethylammonium salt (BzATP), which is known to activate P2X7R. They observed that the expression of P2X7R, NLRP3, and IL‑1β (a pro-inflammatory cytokine) increased in the HNECs following this induction.

Next, the researchers explored the therapeutic effect of a selective P2X7R antagonist called A740003 on P2X7R, NLRP3 inflammasome, and IL‑1β alterations in HNECs. They employed techniques such as enzyme‑linked immunosorbent assay, WB, and PCR to analyze the changes. They found that the expression of NLRP3 and IL‑1β decreased in the HNECs after treatment with A740003.

Based on these findings, the study suggests that the activation of P2X7R-mediated NLRP3 inflammasome may play a role in the pathogenesis of CRSwNP. The overexpression of P2X7R in CRSwNP, along with the upregulation of NLRP3 and IL‑1β in HNECs after inflammatory stimulation, supports the involvement of P2X7R and the NLRP3 inflammasome in the inflammation process associated with CRSwNP.

It is important to note that this summary is based on a hypothetical study and the information provided may not correspond to actual research findings.