Interleukin-19 enhances eosinophil infiltration through upregulation of epithelium-derived RANTES expression via the ERK/NF-κB signalling pathway in patients with eosinophilic CRSwNP

• Published in: Inflammation research Vol. 73; no. 4; pp. 499 - 513
• Main Authors: Huang, Zizhen, Li, Xia, Li, Yue, Huang, Weiqiang, Lai, Xiaoping, Wu, Haotian, Chen, Xiaohong, Zhang, Yana, Chang, Lihong, Zhang, Gehua
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01.04.2024; Springer Nature B.V
• Subjects: Allergology; Antibodies; Biomedical and Life Sciences; Biomedicine; Blocking antibodies; Cell activation; Chemokines; Confocal microscopy; Cytokines; Dermatology; Enzyme-linked immunosorbent assay; Eosinophil cationic protein; Eosinophils; Epithelial cells; Epithelium; Immunofluorescence; Immunohistochemistry; Immunology; Infiltration; Interleukin 19; Interleukins; Leukocyte migration; Leukocytes (eosinophilic); Neurology; NF-κB protein; Original Research Paper; Pharmacology/Toxicology; Phosphorylation; Polyps; RANTES; Receptors; Rheumatology; Rhinosinusitis; Signal transduction; siRNA; Tissues; Up-regulation; Western blotting; Nasal epithelium; Chronic rhinosinusitis with nasal polyps; IL-19; RANTES; Eosinophil
• ISSN: 1023-3830; 1420-908X; 1420-908X
• DOI: 10.1007/s00011-024-01851-2

Backgroud The recurrence rate of chronic rhinosinusitis with nasal polyps (CRSwNP) is positively correlated with eosinophil infiltration. Increased interleukin (IL)-19 and eosinophil chemokine RANTES levels have been reported in patients with CRSwNP. This study aimed to clarify the role of IL-19 in mediating RANTES expression and eosinophilic infiltration in eosinophilic CRSwNP (Eos CRSwNP). Methods Nasal tissue samples were obtained from patients with CRSwNP and controls. The expression of IL-19, its receptors, ECP, and RANTES in tissues was investigated. Primary human nasal epithelial cells (HNECs) and nasal polyp tissue blocks were cultured, then stimulated by IL-19; ERK phosphorylation, NF-κB pathway activation, RANTES level, eosinophils migration and infiltration were detected using RT-qPCR, ELISA, western blotting, HE, immunohistochemistry, immunofluorescence staining, confocal microscopy, and transwell migration assay. Results The expression of IL-19 and its receptors (IL-20R1/IL-20R2), eosinophil cationic protein, and RANTES in nasal tissues from patients with Eos CRSwNP was significantly increased compared to that in non-Eos CRSwNP and control subjects. IL-19 co-localized with RANTES in nasal tissues and significantly elevated RANTES expression in HNECs. IL-19-blocking antibody and siRNA knockdown of IL-20R1 ameliorated the effect of IL-19 on RANTES secretion in HNECs. Moreover, IL-19-induced RANTES upregulation was associated with the activation of the ERK and NF-κB pathways. NF-κB activation was mediated by the ERK pathway in IL-19-treated HNECs, and IL-19 enhanced eosinophil infiltration in nasal polyp tissue blocks. Conclusions Our findings indicate that IL-19 promotes RANTES expression via the ERK/NF-κB pathway in HNECs and is implicated in eosinophil infiltration in patients with Eos CRSwNP.