Vam3 Anti-asthma Inflammation And Airway Remodeling Effect And Mechanism Study

Vam3 is an active component isolated from the extract of Vitis amurens.The previous work has displayed the significant effect of Vam3 on the asthmatic inflammation.In this study,an asthma model was established to explore the effects and mechanisms of Vam3 and to explain the potential effects of Vam3 on the airway remodeling.Histamine-induced guinea pig model was used to investigate the anti-acute inflammatory effects of Vam3. It was found that Vam3 could prolong latency period for the onset of spasm on guinea pigs and decrease the cell infiltration in the lung.BALB/c mice were challenged by OVA inhalation. Lung tissue were stained with Mayer's hematoxylin and eosin for histopathologic examination. Bronchoalveolar lavage were performed to detect the cell infiltration in the lung. The level of IL-4 in bronchoalveolar lavage fluid (BALF) was measured using ELISA method. The expression of ICAM-1 in the lung were analyzed by western blot and immunohistochemistry method.The spleen cells were immunostained with phycoerythrin(PE)-conjugated anti-CD8 mAb and fluorescein isothiocyanate (FITC)-conjugated anti-CD4mAb for assessment of T cell subset differentiation. It was found that Vam3 could inhibit the expression of ICAM-1 in the OVA-induced mouse model.The effects of Vam3 on MMP-9 activity in LPS,TNF-a,PMA induced-THP-1 cell were determined by gelatin zymography. It was found that Vam3 could significantly suppress the activity of MMP-9 induced by LPS, TNF-α, PMA in THP-1 cell.A549 cells were transiently transfected with the NF-κB reporter plasmid.The effects of Vam3 on LPS, TNF-a, PMA induced-NF-κB signaling pathway in transfected A549 cell were detected by luciferase assay.It was found that Vam3 could reduced LPS, TNF-a, PMA-induced NF-KB-dependent luciferase enzyme expression.The effect of Vam3 on proliferation of vascular smooth muscle cell was detected by MTT assay.It was found that Vam3 could signifiantly inhibit the proliferation of vascular smooth muscle cell induced by PMAThe results demonreate that (1)Vam3 displayed anti-inflammatory and anti-airway remodeling effects.(2) Vam3 may inhibit expression the cytokines involved in asthma by down-regulating NF-κB activity.(3)Vam3 may have anti-airway remodeling effects by inhibiting MMP-9 activity and proliferation of smooth muscle cell...