Eosinophil-derived TGF beta 1 controls the new bone formation in chronic rhinosinusitis with nasal polyps

Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) is characterized by chronic eosinophilic inflammation and new bone formation (NBF). These processes may be associated with each other in the pathogenesis and influence the severity and prognosis of the disease. However, it is still unclear how eosinophilic inflammation is involved in the NBF. Methodology: Sinus bone cells were isolated from ethmoid bone tissues of patients with CRSwNP and controls. Transforming growth factor beta 1 (TGF beta 1) and alkaline phosphatase (ALP) expression in sinus bone cells was determined using quantitative RT-PCR, immunoblotting, and immunohistochemistry. The co-localization of TGF beta 1 with eosinophils was assessed by immunofluorescence staining. Sinus bone cells were co-cultured with eosinophils (Eol-1 cell line), which were differentiated with butyrate, to measure the osteoblast differentiation activity of sinus bone cells. Results: TGF beta 1 expression was increased in sinus bone tissues and correlated with CT scores in CRSwNP. TGF beta 1 was also increased in the submucosa of CRSwNP and co-localized predominantly with eosinophils compared with neutrophils Differentiated Eol-1 cells-derived TGF beta 1 increased ALP expression in sinus bone cells. Treatment with a TGF beta 1 inhibitor attenuated TGF beta 1-induced ALP expression and staining in sinus bone cells of CRSwNP, leading to loss of bone formation. Conclusions: Eosinophil-derived TGF beta 1 was enriched in the submucosa of CRSwNP, which induced ALP expression in sinus bone cells and NBF. Therefore, eosinophil-derived TGF beta 1 may mediate aberrant bone remodeling in CRSwNP.