Abstract
BackgroundCRSwNP is an inflammatory disease but the mechanism is not yet fully understood. MiR-21, a member of miRNAs, has been reported to play roles in mediating inflammation. However, the expression of miR-21 and its role in patients with CRSwNP remain elusive.MethodsTurbinates from control subjects, uncinate processes from CRSsNP, polyp tissues from CRSwNP, and nasal epithelial cells brushed from nasal mucosa were collected. The expression of miR-21 and cytokines in nasal tissues and epithelial cells were detected by qPCR. The localization of miR-21 was detected by ISH, and its target was identified by bioinformation analysis, qPCR, IHC, WB, and luciferase reporter system. The protein and mRNA of PDCD4 and NF-κB P65 were determined by WB and qPCR after miR-21 transfection in HNEpC. The role of miR-21 on cytokines was analyzed in HNEpC and nasal polyp explants.ResultsMiR-21 was upregulated in CRSwNP relative to control subjects by qPCR, which was determined mainly in nasal epithelial cells of CRSwNP by ISH. Both pro-inflammation cytokines (IL-1β, IL-6, IL-8, IL-25, and TSLP) and a suppressive cytokine (IL-10) were overexpressed in the epithelial cells of CRSwNP. The expression of miR-21 was positively correlated with IL-10 and negatively correlated with IL-6, IL-8, IL-33, and TSLP in the epithelial cells of CRSwNP. As a potential target of miR-21, the expression of PDCD4 was negatively correlated with miR-21 in CRSwNP. In HNEpC, miR-21 could reduce the expression of PDCD4 at both mRNA and protein levels, and bioinformation analysis and luciferase reporter system confirmed PDCD4 as one target of miR-21. Furthermore, miR-21 could decrease the activation of NF-κB and increase IL-10 mRNA. Both SEB and LPS could elevate miR-21, with IL-25, IL-33, TSLP induced by SEB and IL-1β, IL-6, IL-8 induced by LPS, while the miR-21 could regulate the expression of IL-33, TSLP, IL-1β, IL- 6 and IL-8 in vitro and ex vivo. Clinically, miR-21 expression was inversely correlated with the Lund-Mackay CT scores and the Lund-Kennedy scores in CRSwNP.ConclusionMiR-21 could be a prominent negative feedback factor in the inflammation process to attenuate the expression of pro-inflammatory cytokines, thereby playing an anti-inflammation role in CRSwNP.
Highlights
Chronic rhinosinusitis (CRS) is a common inflammatory disease with approximately 10% of the adult population affected all over the world [1, 2]
MiR-21 could be a prominent negative feedback factor in the inflammation process to attenuate the expression of pro-inflammatory cytokines, thereby playing an anti-inflammation role in CRS with NP (CRSwNP)
To determine the expression level of miR-21, we performed a quantitative PCR (qPCR) assay among 15 control subjects, 10 patients with CRSsNP, and 45 patients with CRSwNP according to the method described previously [27]
Summary
Chronic rhinosinusitis (CRS) is a common inflammatory disease with approximately 10% of the adult population affected all over the world [1, 2]. The nasal epithelium is exposed to a variety of stimuli like SEB and LPS, which cause dysfunction of the epithelium barrier and activation of epithelial cells. Cytokines, such as IL-1b, IL- 6, IL-8, IL-25, IL-33, and TSLP are secreted by activated epithelial cells and can affect numerous immune cells, inciting inflammatory responses [6,7,8]. IL-10 is an anti-inflammatory cytokine that can limit and terminate inflammatory responses and could be expressed by nasal epithelial cells [10, 11]. The expression of miR-21 and its role in patients with CRSwNP remain elusive
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