Endothelin-1 (ET-1) is a potent vaso and bronchoconstrictor. We have previously shown that in the presence of ET-1 bronchial epithelial cells migrate more slowly. Connective tissue growth factor (CTGF) is a cysteine rich secreted protein and regulates fibrosis. In addition, we have previously shown that CTGF is expressed in airway epithelial cells under the conditions of stress starvation. The aim of this study was to describe the effect of ET-1 on CTGF expression, using a lung epithelial-fibroblast co-culture system. Bronchial epithelial cells (BEC) were grown and stimulated with ET-1, 100ng/ml of media, for 24 hours. At 0, 4 and 24 hours, total RNA was isolated. Reverse transcription PCR was performed and CTGF transcripts were semi-quantified. In addition, BEC were grown in co-culture, in the presence of human lung fibroblasts (FB). The same experiment was conducted for FB grown in the presence or absence of ET-1. Control cells were grown only in the basal media. At both time points, following exposure to ET-1, BEC expressed more CTGF as compared to control. Cells in co-culture with FB, expressed no CTGF at 4 hours, and detectable CTGF at 24 hours. CTGF was detected at all time points for FB in both control and stimulated cells. ET-1 induces expression of CTGF in BEC as compared to control. ET-1 may be an important regulator of CTGF expression in the airway. Lung fibroblasts may secrete epithelial cell regulatory factors, controlling the expression of CTGF in the presence of ET-1.

Chronic allograft dysfunction is a leading cause of allograft failure, morbidity and mortality following solid organ transplantation. The pathogenesis of chronic allograft failure has a final common pathway leading to organ fibrosis. Pirfenidone is an effective and novel anti-fibrotic agent with anti-inflammatory properties. Clinical use of the agent has been tested in a number of non-transplant recipients and has a favorable safety profile based on available clinical data. Building on these observations and findings, and considering the role of fibrosis in chronic allograft rejection, Pirfenidone (PFD) was initially investigated as adjunctive therapy in a rat heterotopic tracheal transplantation model. This led to several studies which confirmed that PFD may well be worth considering for further investigation. This paper reviews the possibility of using PFD in clinical transplantation management.