[Role of roxithromycin on glucocorticoid resistance of human bronchial epithelial cells and its mechanism].

Objective: To explore the effects of roxithromycin (RXM) on glucocorticoid resistance of human bronchial epithelial cells exposed to smoke and its mechanism. Methods: Beas-2B cells as the research object were grouped into: control group, 10%cigarette smoke extract (CSE) group, roxithromycin (RXM)+ 10%CSE group. With 10%CSE intervention in the 10%CSE group, 10%CSE and RXM intervention in the RXM+ 10%CSE group, complete culture solution intervention in the control group. Interleukin-8 (IL-8) levels were measured by enzyme linked immunosorbent assay (ELISA) and IL-8 inhibition rate and dexamethasone half inhibitory concentration (IC50-Dex) were calculated; the expression of histone deacetylase 2 (HDAC2) protein was detected by immunofluorescence (IF) and Western blotting (WB). Results: In response to dexamethasone at the concentration of 10(-9,) 10(-8,) 10(-7) and 10(-6) mol/L successively, the IL-8 inhibition rates of RXM+ 10%CSE group [(27.55±3.81)%, (49.60±1.45)%, (55.36±3.36)%, (60.32±3.13)%, respectively] were lower than those of control group [(32.85±2.56)%, (57.12±2.81)%, (60.81±2.08)%, (67.24±3.50)%, respectively], but higher than those of 10%CSE group [(19.15±1.69)%, (37.02±2.30)%, (47.15±2.01)%, (52.09±1.57)%, respectively] (all P<0.05). In contrast, the IC50-Dex of RXM+ 10%CSE group [(4.94±1.62)×10(-8)] was significantly higher than that of control group [(1.75±0.77)×10(-8)], but lower than that of 10%CSE group [(2.92±0.78)×10(-7)] (both P<0.01). The expression of HDAC2 protein of 10%CSE group (0.011±0.004 from IF and 0.46±0.10 from WB) was lower than that of control group (0.037±0.005 and 0.91±0.06, correspondingly), while RXM+ 10%CSE group (0.025±0.005 and 0.77±0.09, correspondingly) was lower than that of control group but higher than that of 10%CSE group (all P<0.05). Conclusion: Roxithromycin may restrain tobacco smoke exposure-induced glucocorticoid resistance in human bronchial epithelial cells through upregulating HDAC2 expression.