The Expression Of HDAC2 In Nasal Polyps And Its Role In The Sensitivity Of Steroid Treatment

Objectives:To analyze the expression of HDAC2 in the nasal polyps and its role in regulating the anti-inflammatory effect of steroid in the nasal epithelial cells.Methods:Patients who were diagnosed as nasal polyps were followed up in the outpatient department after functional endoscopic sinus surgery.28 adult patients were involved in our study, including 13 recurrent patients and 15 non-recurrent patients. The expression of HDAC2 in nasal polyps and normal nasal mucosa were investigated with immunohistochemistry and the relationship between smoking and HDAC2 was also analyzed.0.05% protease XIV was used to digest the nasal mucosa for the nasal epithelial cells culture. IL-1β with or without FP was used to stimulate nasal epithelial cells and cell supernatants were collected after 24 hours stimulation. Enzyme linked immunosorbent assay (ELISA) was used to measure the level of IL-6 and IL-8 in cell supernatants. In addition, HDACs inhibitor (TSA) or siRNA which was specific for HDAC2 was used to reduce HDAC2 activity in the nasal epithelial cells. The efficacy of siRNA was confirmed by western blot. The cell supernatants were also collected. Enzyme linked immunosorbent assay (ELISA) was used to measure the level of IL-6 and IL-8 in cell supernatants.Results:HDAC2 was located in both epithelium layer and lamina propria of nasal polyps and normal mucosa. The expression of HDAC2 in the epithelium and lamina propria were significantly lower than that of normal mucosa (P<0.05). However, the expression of HDAC2 in recurrent nasal polyps and non-recurrent nasal polyps showed no significant difference. Smoking had no effect on the expression of HDAC2. The nasal epithelial cells were successfully cultured in vitro and displayed typical cobblestone-like morphology under inverted microscope. The primary cells can be sub-cultured about 8th day after primary culture. The epithelial cells of passages 2 and 3 keep cobblestone-like morphology and proliferation. Nasal epithelial cells could be activated after IL-1β stimulation characterized by significantly increased level of IL-6 as well as IL-8.The gradient concentration FP (10-6-10-10M) could inhibit the secretion of IL-6 and IL-8.The HDACs inhibitor (TSA) or siRNA-HDAC2 could reduce the anti-inflammatory effect of FP through inhibiting the expression of HDAC2 which was confirmed by western blot.Conclusions:The low expression of HDAC2 in nasal polyps may play a role in the pathogenesis of nasal polyps. The anti-inflammatory effect of steroid in nasal epithelial cells was in part dependent on the HDAC2.