Expression and clinical significance of VCAM-1, IL-6, and IL-17A in patients with allergic rhinitis

Gao, Simin; Yu, Liang‐Cai; Zhang, Jin; Li, Xiaoying; Jin, Zhou; Zeng, Ping; Zhang, Xiaoqing

doi:10.21037/apm-21-546

Cited by 15 publications

(16 citation statements)

References 14 publications

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“…Prior research has also often adopted the above indicators for observation of the pathological development of AR [ 21 , 22 ]. Similar to prior research [ 23 , 24 ], the times of sneezing and rubbing the nose, IgE, IL-4, IL-6, and HA levels in the AR group all greatly increased in our study, which can also verify the success of modelling. As everyone knows, IgE is a crucial factor that mediates allergic inflammatory diseases of the respiratory tract, which is primarily produced by plasma cells in the mucosa lamina propria of the respiratory tract and digestive tract [ 25 ].…”

Section: Discussionsupporting

confidence: 90%

Influences of miR-378a-3p on the Pathogenesis of Allergic Rhinitis via GzmB-Mediated Inflammatory Reaction

Wang

Zhang

2022

Evidence-Based Complementary and Alternative Medicine

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Background and objective. Allergic rhinitis (AR), a highly frequently seen chronic inflammation of the upper respiratory tract, shows a growing global incidence. The modern research on the pro-inflammatory mechanism molecularly offers a new direction for the early therapy AR in the future and also reveals the potential therapeutic targets of IT, which is known as the breakthrough of diagnosis and therapy of AR. Through the screening of GSE43523 data set in GEO, we discovered aberrant expression of granzyme B (GzmB) gene in AR cases. Online data analysis revealed the possible regulation of upstream target microRNA-378a-3p (miR-378a-3p) on its expression. Accordingly, this study analysed the impacts of miR-378a-3p and GzmB on AR to set the foundation for the follow-up associated research and offer novel ideas and directions for the future diagnosis and therapy of AR. Methods. Totally, 24 BALB/c mice were assigned to the AR group, control group, GzmB group, and blank group (each n = 6). The blank group was normally fed without treatment, and the other three groups were treated by ovalbumin (OVA) to induce AR models, in which the GzmB group was intranasally injected with lentiviral vector suppressing GzmB expression during the second immunization, while the control group was given the GzmB-blank vector. The times of AR pathological behaviours such as sneezing and scratching the nose of mice were observed and counted. The nasal lavage fluid of each mouse was acquired, and then, the mouse was executed by cervical dislocation, followed by collection of blood and nasal mucosa tissues. Then, ELISA was adopted for quantifying immunoglobulin E (IgE), interleukin (IL)-4, IL-6, and histamine (HA), and nasal mucosa tissues were treated by HE and TUNEL staining to observing their histopathological manifestations. PCR and western blot (WB) were adopted for quantifying GzmB and miR-378a-3p. Additionally, with NP69 cells, dual luciferase reporter (DLR) assay was carried out for determining the targeting association of GzmB with miR-378a-3p. Another 24 mice were assigned to the AR group, GzmB group, miR-378a-3p group, and GzmB+ miR-378a-3p group (each n = 6). The AR and GzmB groups were treated as above. The miR-378a-3p group was intervened by lentiviral vector suppressing miR-378a-3p, while the GzmB+ miR-378a-3p group was given GzmB and lentiviral vector suppressing miR-378a-3p meantime. A rescue assay was conducted through repeating the above tests. Results. The times of sneezing and rubbing the nose and the levels of IgE, IL-4, IL-6, and HA were similar between the control and AR groups (all P > 0.05 ), and these items of the two groups were all higher than those of the blank and GzmB groups (all P < 0.05 ). However, no notable difference was observed in IL-4 and IL-6 levels between the GzmB and blank groups (both P > 0.05 ), while higher levels of other detection results were found in the former group than in the latter (all P < 0.05 ). The staining results revealed obvious congestion, oedema, and necrosis structures in the nasal mucosa epithelium of the control and AR groups and also revealed a large number of infiltrating eosinophils and notable increase of apoptotic nasal mucosa epithelial cells. The GzmB group showed notably improved nasal mucosa tissues, and its infiltration and apoptosis of eosinophils were more notable than those of the blank group, but notably weaker than those of the AR and control groups. Additionally, the PCR and WB results revealed similar miR-378a-3p and GzmB levels in nasal mucosa between the control and AR groups (both P > 0.05 ), and a notable decrease of miR-378a-3p and a notable increase of GzmB in both groups (both P < 0.05 ). The DLR assay revealed notably suppressed fluorescence activity of GzmB-WT in NP69 cells after transfection of miR-378a-3p mimics ( P < 0.05 ) and notably down regulated GzmB protein after increase of miR-378a-3p (P<0.05). Finally, the rescue assay revealed that downregulating miR-378a-3p aggravated the pathological changes of AR ( P < 0.05 ) and also completely reversed the impacts of inhibiting GzmB on the pathological behaviours of AR mice. Conclusions. MiR-378a-3p can accelerate the pathological development of AR through targeted inhibition on the release of pro-inflammatory factors such as IgE and HA activated by GzmB, so it is a promising molecular target of AR therapy and offers a novel research direction for the complete cure of AR.

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Section: Discussionsupporting

confidence: 90%

Influences of miR-378a-3p on the Pathogenesis of Allergic Rhinitis via GzmB-Mediated Inflammatory Reaction

Wang

Zhang

2022

Evidence-Based Complementary and Alternative Medicine

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“…IL6 is also involved in the pathophysiology of allergic diseases, and high levels of IL-6 in the blood promote the release of allergic mediators and exacerbate allergic rhinitis [ 36 , 37 ]. In addition, it has been suggested that the allergic rhinitis symptoms are alleviated by inhibiting the higher IL-6 expression level [ 38 ], which is a result supporting the pharyngeal allergic inhibitory effect of EAT [ 2 ]. Similar to IL-6, we showed that EAT downregulates the mRNA expression of tumor necrosis factor alpha (TNFα), one of the most crucial proinflammatory cytokines, along with IL-6 ( Figure 4 ).…”

Section: Discussionmentioning

confidence: 99%

Epipharyngeal Abrasive Therapy (EAT) Reduces the mRNA Expression of Major Proinflammatory Cytokine IL-6 in Chronic Epipharyngitis

Nishi

Yoshimoto

Nishi

et al. 2022

IJMS

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The epipharynx, located behind the nasal cavity, is responsible for upper respiratory tract immunity; however, it is also the site of frequent acute and chronic inflammation. Previous reports have suggested that chronic epipharyngitis is involved not only in local symptoms such as cough and postnasal drip, but also in systemic inflammatory diseases such as IgA nephropathy and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and Long COVID. Epipharyngeal Abrasive Therapy (EAT), which is an effective treatment for chronic epipharyngitis in Japan, is reported to be effective for these intractable diseases. The sedation of chronic epipharyngitis by EAT induces suppression of the inflammatory cytokines and improves systemic symptoms, which is considered to be one of the mechanisms, but there is no report that has proved this hypothesis. The purpose of this study was to clarify the anti-inflammatory effect of EAT histologically. The study subjects were 8 patients who were not treated with EAT and 11 patients who were treated with EAT for chronic epipharyngitis for 1 month or more. For immunohistochemical assessment, the expression pattern of IL-6 mRNA, which plays a central role in the human cytokine network, was analyzed using in situ hybridization. The expression of IL-6 in the EAT-treated group was significantly lower than those in the EAT nontreated group (p = 0.0015). In addition, EAT suppressed the expression of tumor necrosis factor alpha (TNFα), a crucial proinflammatory cytokine. As a result, continuous EAT suppressed submucosal cell aggregation and reduced inflammatory cytokines. Thus, EAT may contribute to the improvement of systemic inflammatory diseases through the suppression of IL-6 expression.

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“…Increasing evidence suggests that ICAM-1 and VCAM-1 enhance the inflammatory response and are involved in various diseases (69)(70)(71)(72). It has been well known that ICAM-1 and VCAM-1 play roles in arresting immune cells and initiating TEM, which plays an essential step in the development of atherosclerosis.…”

Section: Rt-pcr Analyses Confirmed the Expression Of Integrins Avb3mentioning

confidence: 99%

Human IL-32θA94V mutant attenuates monocyte-endothelial adhesion by suppressing the expression of ICAM-1 and VCAM-1 via binding to cell surface receptor integrin αVβ3 and αVβ6 in TNF-α-stimulated HUVECs

Park

Kim

et al. 2023

Front. Immunol.

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Interleukin-32 (IL-32), first reported in 2005, and its isoforms have been the subject of numerous studies investigating their functions in virus infection, cancer, and inflammation. IL-32θ, one of the IL-32 isoforms, has been shown to modulate cancer development and inflammatory responses. A recent study identified an IL-32θ mutant with a cytosine to thymine replacement at position 281 in breast cancer tissues. It means that alanine was also replaced to valine at position 94 in amino acid sequence (A94V). In this study, we investigated the cell surface receptors of IL-32θA94V and evaluated their effect on human umbilical vein endothelial cells (HUVECs). Recombinant human IL-32θA94V was expressed, isolated, and purified using Ni-NTA and IL-32 mAb (KU32-52)-coupled agarose columns. We observed that IL-32θA94V could bind to the integrins αVβ3 and αVβ6, suggesting that integrins act as cell surface receptors for IL-32θA94V. IL-32θA94V significantly attenuated monocyte-endothelial adhesion by inhibiting the expression of Intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in tumor necrosis factor (TNF)-α-stimulated HUVECs. IL-32θA94V also reduced the TNF-α-induced phosphorylation of protein kinase B (AKT) and c-jun N-terminal kinases (JNK) by inhibiting phosphorylation of focal adhesion kinase (FAK). Additionally, IL-32θA94V regulated the nuclear translocation of nuclear factor kappa B (NF-κB) and activator protein 1 (AP-1), which are involved in ICAM-1 and VCAM-1 expression. Monocyte-endothelial adhesion mediated by ICAM-1 and VCAM-1 is an important early step in atherosclerosis, which is a major cause of cardiovascular disease. Our findings suggest that IL-32θA94V binds to the cell surface receptors, integrins αVβ3 and αVβ6, and attenuates monocyte-endothelial adhesion by suppressing the expression of ICAM-1 and VCAM-1 in TNF-α-stimulated HUVECs. These results demonstrate that IL-32θA94V can act as an anti-inflammatory cytokine in a chronic inflammatory disease such as atherosclerosis.

show abstract

Expression and clinical significance of VCAM-1, IL-6, and IL-17A in patients with allergic rhinitis

Cited by 15 publications

References 14 publications

Influences of miR-378a-3p on the Pathogenesis of Allergic Rhinitis via GzmB-Mediated Inflammatory Reaction

Influences of miR-378a-3p on the Pathogenesis of Allergic Rhinitis via GzmB-Mediated Inflammatory Reaction

Epipharyngeal Abrasive Therapy (EAT) Reduces the mRNA Expression of Major Proinflammatory Cytokine IL-6 in Chronic Epipharyngitis

Human IL-32θA94V mutant attenuates monocyte-endothelial adhesion by suppressing the expression of ICAM-1 and VCAM-1 via binding to cell surface receptor integrin αVβ3 and αVβ6 in TNF-α-stimulated HUVECs

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