Increased expression of interleukin 36 in chronic rhinosinusitis and its contribution to chemokine secretion and increased epithelial permeability

Joo, Young Ho; Kim, Ha Kyun; Choi, In Taek; Han, Hae Min; Lee, Ki Jeong; Kim, Tae Hoon; Lee, Sang Hag

doi:10.1016/j.cyto.2019.154798

Cited by 9 publications

(11 citation statements)

References 38 publications

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“…Furthermore, upregulated levels of IL-8 were noted in nasal lavage fluid obtained from asthmatic patients after RV infection, in contrast to levels found in healthy individual ( 51 ). Our previous studies showed that chemokines, including CXCL1, CXCL2, and IL-8, were upregulated in cultured epithelial cells obtained from patients with CRS ( 52 ). In this respect, blocking ephA2 receptor could provide protective influences in the airway, suppressing unwanted inflammatory responses.…”

Section: Discussionmentioning

confidence: 99%

The Expression of ephrinA1/ephA2 Receptor Increases in Chronic Rhinosinusitis and ephrinA1/ephA2 Signaling Affects Rhinovirus-Induced Innate Immunity in Human Sinonasal Epithelial Cells

et al. 2021

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EphA2 receptor and its ephrin ligands are involved in virus infection, epithelial permeability, and chemokine secretion. We hypothesized that ephrinA1/ephA2 signaling participates in rhinovirus (RV)-induced antiviral immune response in sinonasal mucosa of patients with chronic rhinosinusitis (CRS). Therefore, we investigated the expression of ephrinA1/ephA2 in normal and inflamed sinonasal mucosa and evaluated whether they regulate chemokine secretion and the production of antiviral immune mediators including interferons (IFNs) in RV-infected human primary sinonasal epithelial cells. For this purpose, the expression and distribution of ephrinA1/ephA2 in sinonasal mucosa were evaluated with RT-qPCR, immunofluorescence, and western blot. Their roles in chemokine secretion and the production of antiviral immune mediators such as type I and III IFNs, and interferon stimulated genes were evaluated by stimulating ephA2 with ephrinA1 and inactivating ephA2 with ephA2 siRNA or inhibitor in cells exposed to RV and poly(I:C). We found that ephrinA1/ephA2 were expressed in normal mucosa and their levels increased in inflamed sinonasal mucosa of CRS patients. RV infection or poly(I:C) treatment induced chemokine secretion which were attenuated by blocking the action of ephA2 with ephA2 siRNA or inhibitor. The production of antiviral immune mediators enhanced by rhinovirus or poly (I:C) is increased by blocking ephA2 compared with that of cells stimulated by either rhinovirus or poly(I:C) alone. In addition, blocking ephA2 attenuated RV replication in cultured cells. Taken together, these results describe a novel role of ephrinA1/ephA2 signaling in antiviral innate immune response in sinonasal epithelium, suggesting their participation in RV-induced development and exacerbations of CRS.

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Section: Discussionmentioning

confidence: 99%

The Expression of ephrinA1/ephA2 Receptor Increases in Chronic Rhinosinusitis and ephrinA1/ephA2 Signaling Affects Rhinovirus-Induced Innate Immunity in Human Sinonasal Epithelial Cells

et al. 2021

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“…IL‐36 is poorly studied in CRS. Joo demonstrated that IL‐36 is expressed in epithelial cells of nasal polyps and may act as a responder to microbial and nonmicrobial elements, 8 Wang et al 9 found that IL‐36γ may exaggerate neutrophilic inflammation in CRS. Because these data suggested IL‐36 might regulate the inflammation and matrix remodelling, we explored the possibility that IL‐36 might participate in EMT of nasal polyps and induce collagen protein production.…”

Section: Discussionmentioning

confidence: 99%

“…IL‐36 family members are dysregulated in inflammatory diseases such as psoriasis, 6 the expression of IL‐36 is related to the prognosis and may be used as a therapeutic target in psoriasis 7 . Joo et al 8 found that CRS epithelial cells expressed IL‐36α, IL‐36β and IL‐36γ. Among them, IL‐36γ is the most abundant isoform, IL‐36γ may exacerbate neutrophilic inflammation in CRS, and the effect of IL‐36γ is not inhibited by dexamethasone 9 .…”

Section: Introductionmentioning

confidence: 99%

The role of interleukin 36γ in the epithelial–mesenchymal transition process of chronic rhinosinusitis: A pilot study

Shen

Chen

Guo

2023

Clinical Otolaryngology

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Purpose: Epithelial-mesenchymal transition (EMT) is an important characteristic in the remodelling of chronic rhinosinusitis with nasal polyps (CRSwNP). IL-36γ and fibroblast activation protein (FAP) may exacerbate remodelling in CRS. Here, we aimed to determine whether IL-36γ and FAP expression are associated with EMT and may be a predictor for CRSwNP prognosis.Methods: Fifty-two non-Eos CRSwNP patients and 12 control patients were obtained and were followed up for more than 1 year after surgery. IL-36γ, FAP and EMT markers expression were evaluated by real-time polymerase chain reaction and western blot.Masson trichrome staining was adopted to assess tissue fibrotic changes. Furthermore, the soluble form of IL-36γ and FAP in nasal secretions was detected by ELISA.Results: While basal expression of E-cadherin decreased, the expression of IL-36γ, vimentin and FAP increased in nasal polyps. In well-prognosis patients, the expression of IL-36γ, vimentin and FAP were significantly decreased than in poor-prognosis patients, while the protein expression of E-cadherin was increased. The protein expression of IL-36γ was notably increased in recurrent nasal polyps than in preoperation specimens. A positive relationship between IL-36γ and FAP expression, a negative relationship between IL-36γ and E-cad expression was noted. The soluble form of IL-36γ and FAP increased during the development of non-Eos CRSwNP, with the highest level in poor-prognosis patients after surgery. Conclusion:Non-Eos CRSwNP have partially undergone EMT under baseline conditions. IL-36γ and FAP expression were related with EMT, the soluble form of IL-36γ and FAP in nasal secretions may predict the prognosis of patients.

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“…In addition, vasculopathy and lymphoid infiltrate of the superficial and deep dermis is main cutaneous manifestations in COVID-19 patient (96)(97)(98)(99). It was reported that ACE2 and SARS-CoV-2 RNA can be detected in the blood vessels (100,101), whereas IL-36g and IL-36R also expressed in human dermal microvascular endothelial cells (HDMEC) (18,102,103). It is likely that SARS-CoV-2 infection in endothelia cells may induce IL-36 secretion, leading to leukocytes infiltration and skin symptoms in COVID-19 patients.…”

Section: Il-36 As a Therapeutic Target Of Covid-19mentioning

confidence: 99%

The Role of IL-36 in Infectious Diseases: Potential Target for COVID-19?

Wang

Liang

2021

Front. Immunol.

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IL-36 is a member of the interleukin 1 cytokine family, which is currently experiencing a renaissance due to the growing understanding of its context-dependent roles and advances in our understanding of the inflammatory response. The immunological role of IL-36 has revealed its profound and indispensable functional roles in psoriasis, as well as in several inflammatory diseases, including inflammatory bowel disease (IBD), systemic lupus erythematosus, rheumatoid arthritis (RA) and cancer. More recently, an increasing body of evidence suggests that IL-36 plays a crucial role in viral, bacterial and fungal infections. There is a growing interest as to whether IL-36 contributes to host protective immune responses against infection as well as the potential implications of IL-36 for the development of new therapeutic strategies. In this review, we summarize the recent progress in understanding cellular expression, regulatory mechanisms and biological roles of IL-36 in infectious diseases, which suggest more specific strategies to maneuver IL-36 as a diagnostic or therapeutic target, especially in COVID-19.

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Increased expression of interleukin 36 in chronic rhinosinusitis and its contribution to chemokine secretion and increased epithelial permeability

Cited by 9 publications

References 38 publications

The Expression of ephrinA1/ephA2 Receptor Increases in Chronic Rhinosinusitis and ephrinA1/ephA2 Signaling Affects Rhinovirus-Induced Innate Immunity in Human Sinonasal Epithelial Cells

The Expression of ephrinA1/ephA2 Receptor Increases in Chronic Rhinosinusitis and ephrinA1/ephA2 Signaling Affects Rhinovirus-Induced Innate Immunity in Human Sinonasal Epithelial Cells

The role of interleukin 36γ in the epithelial–mesenchymal transition process of chronic rhinosinusitis: A pilot study

The Role of IL-36 in Infectious Diseases: Potential Target for COVID-19?

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