Late Breaking Abstract - Bronchial Thermoplasty restores constitutive high PRMT1 expression in asthmatic airways

Abstract

Introduction: Bronchial Thermoplasty (BT) is the only therapeutic method reducing airway remodeling in asthma. Constitutive high expression of protein arginine methyltransferase 1 (PRMT1) and increased mass of mitochondria had been shown in asthmatic airways and promoted airway wall remodeling by increasing proliferation and deposition of extracellular matrix components. Aims: This study investigated the effect of BT on PRMT1 expression in tissue sections and isolated cells obtained from asthma patients before and after BT. Methods: 10 asthma patients were treated with BT according to standard protocol. PRMT1 expression in tissue was evaluated by immunohistochemistry in situ. The effect of BALF on primary lung fibroblasts was determined for: PRMT1 expression, Erk1/2 MAPK activity, Hsp60 expression, and mitochondria mass in vitro. Results: Comparing PRMT1 expression in tissue section obtained before and after BT revealed a significant reduction PRMT1 and Hsp60 expression. BALF collected before BT, stimulated Erk1/2 MAPK activity, PRMT1 and Hsp60 expression as well as mitochondrial mass. BALF collected after BT did not have such a stimulatory effect on fibroblasts and in asthmatic cells it profoundly inhibited the up-regulation of all above-mentioned remodeling associated parameters. Conclusions: The results demonstrated that BT reduces remodeling parameters in vivo and in vitro in asthma patients by restoring PRMT1 expression to normal levels and thereby reduced sub-epithelial mesenchymal cell remodeling activity.