[A study of interferon-gamma induced airway mucous cell apoptosis and its mechanisms].

ABSTRACT

OBJECTIVE: To investigate the effect of interferon-gamma (IFN-gamma) on airway mucous cells and its mechanisms. METHODS: (1) Normal human bronchial epithelial cells (NHBEs) were cultured under specific conditions, and treated by IFN-gamma for 3 days. The cells were analyzed with fluorescein isothiocyanate (FITC) and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay. (2) Twenty wild type C57BL/6J mice were immunized and divided into 4 groups, and treated with IFN-gamma (50 ng and 100 ng, respectively), interleukin-13 (IL-13, 5 microg) and saline by nostril instillation. The mice were sacrificed and the airway mucous cells were analyzed by morphometry and TUNEL assay. RESULTS: (1) IFN-gamma induced apoptosis in NHBEs, which showed condensed nuclei, nuclear and DNA fragmentaion, and were positive by TUNEL assay. Bax was upregulated and translocated from cell plasma to mitochondria under the treatment. (2) Airway mucous cell account in 100 ng IFN-gamma instillation immunized mice group (28 +/- 6 mucous cells/mm basal lamina) was significantly decreased as compared to that in saline (58 +/- 12) and IL-13 (59 +/- 6) instillation groups (all < 0.05). There was no difference among the IFN-gamma 50 ng (48 +/- 11), saline (58 +/- 12) and IL-13 (59 +/- 6) instillation groups (all P > 0.05). TUNEL assay was also positive in airway mucous cells from IFN-gamma instillation mice as compared to saline instillation mice. CONCLUSIONS: IFN-gamma leads to airway mucous cell apoptosis by Bax upregulating and translocation into mitochondria. This might be of significance in the new therapies of asthma.