Peroxisome Proliferator-activated Receptor ¦Ã In Airway Inflammation In Asthma And Reconstruction

Bronchial asthma is a commen respiratory disease with increasing worldwide morbidity. Chronic airway inflammation and remodeling are two key features of asthma, with a complicated interaction between them. In recent studies, it has been discovered that PPARγ was involved in a wide variety of diseases with a complex effect of anti-proliferation, anti-inflammation and anti-remodeling. But the effect and mechanism of PPARγ in asthma were inconsistent by now. To answer this question, studies were performed in vivo and in vitro and the results were presented in 2 parts as belows.Part 1 The effect of PPARγ on the airway inflammation and remodeling in asthma mice.OBJECTIVE: To investigate the effect of PPARγ on the airway inflammation and remodeling in asthma mice. METHODS: BALB/c mice were sensitized and challenged by ovalbum (OVA) to establish the mouse model of chronic asthma. Rosiglitazone or GW9662 was administered by means of nebulization every day during OVA challenging. The inflammatory cell and IL-4 in BALF were measured to evaluate the airway inflammatory level, as well as the airway responsiveness to adenosine or acetylcholine detected in vitro. The remodeling features both in airway wall and vessels were assessed by means of pathological techniques and hydroxyproline assay. The expression of PPARγ was investigated by immunohistochemistry methods and westernblot, and the transcription of TGFβ1 and eotaxin were measured by RT-PCR. RESULTS: A chronic mice asthma model was established by OVA sensitization and challenge, with profound airway inflammation and remodeling, which can be relieved by treatment of rosiglitazone. PPARγ was located at the airway epithelial cell, airway smooth muscle cell and various kinds of inflammation cells in asthma mice. The nuclear PPARγ, not total PPARγ, increased by rosiglitazone, was in an inverse correlation with the transcription of TGFβ1 and eotaxin(r=0.895, 0.954; p<0.01). CONCLUSIONS: PPARγ agonist can relieve the airway inflammation and remodeling by increasing the nuclear location of PPARγ.Part 2 the effect of PPARγ in bronchial epithelial cells and the interaction between PPARγ and glucocorticoid receptor a Objective: To establish primay culture methods for the human bronchial epithelialcells (hBECs) and investigate the interaction between PPARγ and glucocorticoid receptora (GRa). Methods: The hBECs were collected from surgical samples and cultured in BEGM. The expression of PPARγ and GRa in hBECs treated with rosglitazone was measured by westemblot assay, and the transcription of eotaxin and fibronectin1 (FN1) was measured by RT-PCR. Results: With stimulated by TGFβ1 and IL-4, the transcription of eotaxin and FN1 in hBECs was increased as asthma condition. The nulear PPARγ and GRa were both increased after treatment of PPARγ agonist, associated with the reduction of transcription of eotaxinan and FN1. The inhibitation of eotaxin and FN1 was enhanced by combined treatment of two drugs. Conclusion: PPARγ agonist increases the nuclear PPARγ and GRa in consistant with the doses, but not time. There was a synergistic effect between rosiglitazone and budesonie.The results of this study demonstrated that rosigolitazone, a PPARγ agonist, relieved the airway inflammation and remodeling by enhancing the nulear translocation of both PPARγ and GRa. PPARγ was involved in the anti-inflammation and anti-remodeling process for the asthma, and performing a synergistic effect with GRa.