Effect Of Interferon-γ Transgene Expression On ADAM33 In Murine Pulmonary Fibrosis Via Adenoviral Vector

Objective To invetigate the effect of murine interferon-γ(mIFN-γ) trangene expression via adenoviral vector (AdCMVmIFNγ) on ADAM33 expression in bleomycin-induced murine fibrostic lung tissue. Methods Forty-eight male ICR mice were randomized divided into different groups as a negative control (NC) goupe, positive control (PC), AdCMVmIFN-γtransgene treatment (A,B,C), recombinant murine interferon-γtreatment(D,E,F). Except for goupe NC, mice in the rest of other groups were given bleomycin by nasal instillation. The mice in goupe A,B and C were given AdCMVmIFN-γon day 7,14,21 respectively. The mice in goupe D,E,F were given recombinant mIFN-γfor 6 days by intraperitoneal injection on day 7,14,21 respectively. All the mice were sacrificed on day 35, and before then, their tidal volume(Vt), forced expiratory volume in 0.1second/forced vital capacity(FEV0.1/FEV), and static compliance (Cst) were detemined by AniRes2003 animal lung function system. The bronchoalveolar lavage (BAL), serum and lung specimens were recovered. The concentration of mIFN-γin BAL and serum was measured by enzyme-linked immunosorbant assay. The sections of the right lung were stain with hematoxylin-eosin (H-E) and Masson trichome respectively. The capacity of lung fibrosis was detemined by hypdroxyproline(HYP) content in lung tissue. The profile of ADAM33 and IFN-γexpression in lung tissue was identified by semi-quantitative reverse-transcription polymerase chain reaction (RT-PCR) and western blotting. Result (1)The HYP content in lung tissue in all bleomycin treated groupes was significantly higher than that in NC group (P<0.01). Vt and Cst were significantly higher than that in NC group except group B (P<0.05). (2)The mIFN-γconcentration in BALF in group C was significantly higher than thant in any other groups (P<0.01). (3) ADAM33 expression in all the experimental groups except group C was significant higher than that in group NC (P<0.05), and its expression in group PC and A was even more higher (P<0.01). ADAM33 expression was significantly decreased only in group C compared with that in group PC (P<0.01). Its expression was not significant decrease in any other AdCMVmIFNγadministrated groups compared with group PC. Conclusion The data suggested that ADAM33 expression be increased in bleomycin-induced murine fibrostic lung tissue , and downregulated by IFN-γlocally transgene expression in the lung via adenoviral vector, but not the recombinant IFN-γ.