Beta-2 agonist receptor targeting delivery of ARG1 siRNA for chronic asthma

Abstract

Patients with chronic asthma are more likely to have trouble breathing due to persistent inflammation and airway remodeling. There are many factors that induce the T helper (Th) 2-mediated immune reaction. Among them, arginase 1 (ARG1) play a role in the remodeling of the airways. ARG1, the key protein of the Th2 immune reaction has recently been shown to play an important role in airway remodeling. Therefore reducing ARG1 expression by siRNA can inhibit the remodeling of airway. Beta-2 agonist, Isoprenaline has already been used as a treatment for asthma and causes an immediate response to the expansion of the airway muscles. In this study, we investigate synergistic effects of inhibition of ARG1 and Isoprenaline treatment on asthma. The complex is sufficiently small in size, low in toxicity, and stable, so it can be used as a treatment. The complex were transfected very efficiently in Calu-3 cells, bronchoalveolar lavage (BAL) fluid and lung in the chronic asthma model. In the chronic asthma model, BALF immune cells were decreased and collagen content was also decreased. It indicates that ARG1 siRNA / PEI-Isoprenaline complex is effective as a therapeutic agent for chronic asthma.