Cross-Talk Between Human Mast Cells and Epithelial Cells By IgE-Mediated Periostin Production in Eosinophilic Nasal Polyps

Abstract

Periostin is important in Th2 inflammation and tissue remodeling. Its role in chronic rhinosinusitis with nasal polyps (CRSwNP) remains unclear. This study is to investigate the role of periostin in CRSwNP. Expressions of periostin and its receptor, integrin α V, were investigated in NP by IHC, qRT-PCR, and ELISA. Immunohistochemistry and immunocytochemistry were used to determine cellular sources of periostin in NP and a human mast cell line, LAD2. Periostin was upregulated and was positively and negatively correlated with IL-5/CCL-11 and IL-17A/IFN-γ, respectively, in eosinophilic NP (ENP), but not in non-ENP. A positive correlation existed between periostin and Lund-Mackay CT scores (r=0.542, p=0.0392). Tryptase+ cells were a main source of periostin in ENP. Periostin levels correlated positively with total IgE in ENP homogenate (r=0.733, p=0.0025). Furthermore, when LAD2 cells were stimulated with IgE, IL-4, IL-13 or TNF-α, only IgE enhanced the levels of periostin mRNA (20-fold) and protein (48-fold). Confocal microscopy with immunocytochemical staining showed periostin localized to LAD2 granules. Overexpression of integrin αV was detected in epithelial layers of ENP and correlated with the level of periostin. Integrin αV expression was positively associated with thymic stromal lymphopoietin at mRNA and protein levels. Periostin and integrin αV are up-regulated in ENP and correlate with Th2 markers and disease severity. Mast cells may be a source of NP periostin which affects epithelial cells, and be a possible novel target to treat ENP.