Background: Chronic inflammation triggers tissue remodeling of the human nasal epithelium (HNE). In inflammatory conditions, S100A8 and S100A9, damage-related molecular patterns, have potent pro-inflammatory activity, but their effect on tissue remodeling such as squamous metaplasia is not known. Therefore, we aimed to investigate the roles and regulatory mechanisms of S100A8 and S100A9 on tissue remodeling in chronic rhinosinusitis (CRS).
Methods: The expression of S100A8 and S100A9 were confirmed after type 1 and/or 2 cytokines were treated on HNE cells. In addition, the expression of S100A8, S100A9, and their complex calprotectin was confirmed by immunohistochemistry staining and immunofluorescence in the tissues of CRS patients. After treatment with S100A8, S100A9, and calprotectin in cultured HNE cells, RT-PCR, and Western blot were performed. In addition, gene ontology analysis was performed through bulk RNA sequencing.
Results: TNF-α and IL-1β increased the expression of S100A8 and S100A9 in HNE cells. The expression of S100A8 and S100A9 was increased in the squamous epithelium of CRS tissue. Treatment with S100A8 and S100A9 in HNE cells increased the expression of Involucrin and MMP-9. Bulk RNA sequencing analysis showed that S100A9 had an effect on keratinization and inducing the cornified envelope of HNE cells.
Conclusion: S100A8 and S100A9 were associated with tissue remodeling such as squamous metaplasia. However, the S100A9 showed a more pronounced association. Increased expression of S100A8 and S100A9 in CRS tissue, especially squamous epithelium, correlated with disease severity of CRS. Therefore, we suggest that S100A8 and S100A9 are biomarkers reflecting the severity of inflammation in CRS.
