Cold-inducible RNA-binding protein contributes to tissue remodeling in chronic rhinosinusitis with nasal polyps
- 1 February 2021
- Vol. 76 (2), 497-509
- https://doi.org/10.1111/all.14287
Abstract
Background Cold-inducible RNA-binding protein (CIRP) is a newly identified damage-associated molecular pattern molecule. Its roles beyond promoting inflammation and in human diseases are poorly understood. This study aimed to investigate the involvement of CIRP in chronic rhinosinusitis with nasal polyps (CRSwNP). Methods Immunohistochemistry, quantitative RT-PCR, and ELISA were used to detect the expression of CIRP and matrix metalloproteinases (MMPs) in sinonasal mucosal samples and nasal secretions. Human nasal epithelial cells (HNECs) and THP-1 cells, a human monocytic/macrophage cell line, were cultured to explore the regulation of CIRP expression and MMP expression. Results Cytoplasmic CIRP expression in nasal epithelial cells and CD68(+)macrophages in sinonasal tissues, and CIRP levels in nasal secretions were significantly increased in both patients with eosinophilic and noneosinophilic CRSwNP as compared to those in control subjects. IL-4, IL-13, IL-10, IL-17A, TNF-alpha,Dermatophagoides pteronyssinusgroup 1, and lipopolysaccharide induced the production and secretion of CIRP from HNECs and macrophages differentiated from THP-1 cells. CIRP promoted MMP2, MMP7, MMP9, MMP12, and vascular endothelial growth factor A (VEGF-A) production from HNECs, macrophages differentiated from THP-1 cells, and polyp tissues, which was inhibited by the blocking antibody for Toll-like receptor 4, but not advanced glycation end products. The expression of MMPs and VEGF-A in tissues correlated with CIRP levels in nasal secretions in patients with CRSwNP. Conclusions The upregulated production and release of CIRP from nasal epithelial cells and macrophages may contribute to the edema formation in both eosinophilic and noneosinophilic CRSwNP by inducing MMP and VEGF-A production from epithelial cells and macrophages.Funding Information
- National Natural Science Foundation of China (81873694, 81800889, 81630024, 81570899, 81920108011)
This publication has 45 references indexed in Scilit:
- Diversity of T H cytokine profiles in patients with chronic rhinosinusitis: A multicenter study in Europe, Asia, and OceaniaJournal of Allergy and Clinical Immunology, 2016
- Disease-Specific T-Helper Cell Polarizing Function of Lesional Dendritic Cells in Different Types of Chronic Rhinosinusitis with Nasal PolypsAmerican Journal of Respiratory and Critical Care Medicine, 2014
- Features of airway remodeling in different types of Chinese chronic rhinosinusitis are associated with inflammation patternsAllergy, 2012
- Does mucosal remodeling in chronic rhinosinusitis result in irreversible mucosal disease?The Laryngoscope, 2011
- Pathophysiology of Chronic Rhinosinusitis with Nasal PolypAmerican Journal of Rhinology and Allergy, 2011
- Distinct immunopathologic characteristics of various types of chronic rhinosinusitis in adult ChineseJournal of Allergy and Clinical Immunology, 2009
- TGF-β signaling and collagen deposition in chronic rhinosinusitisJournal of Allergy and Clinical Immunology, 2009
- Role of matrix metalloproteinases in chronic rhinosinusitisCurrent Opinion in Allergy and Clinical Immunology, 2008
- Tissue remodelling in upper airways: where is the link with lower airway remodelling?Allergy, 2006
- Rhinosinusitis: Establishing definitions for clinical research and patient careJournal of Allergy and Clinical Immunology, 2004