Effects of 18β-Glycyrrhetinic Acid on Fungal Protease-Induced Airway Inflammatory Responses.

Yun Hee Kim,Seung-Hyo Lee,Dong Eon Kim

doi:10.1155/2018/6461032

Abstract

Airway epithelial cells secrete diverse inflammatory mediators in response to various stimuli. Thus, early regulation of immune responses in the airway epithelium is likely critical for the control of chronic inflammatory diseases. The purpose of the present study was to evaluate the effects of 18β-glycyrrhetinic acid (GA) on inflammatory responses generated in response to a fungal protease allergen that induces epithelial damage. To understand the underlying mechanisms, we also investigated the inhibitory effects of GA on the production of mitochondrial reactive oxygen species (ROS) in the human bronchial epithelial cell line BEAS2B. In this study, GA treatment reduced cytokine production and the human neutrophil cell line HL60 migration through decreased mitochondrial ROS production. In addition, GA significantly reduced inflammatory cell infiltration and cytokine levels in the bronchoalveolar lavage (BAL) fluid of fungal allergen-administered mice. Inhibitory effects of GA are dependent on the mitochondrial ROS/MAPK axis. Moreover, the effect of GA on the regulation of mitochondrial ROS depends on the expression of uncoupling protein-2 (UCP-2). Taken together, GA might represent a potential therapeutic agent for blocking inflammatory responses in airways.

Highlights

The airway epithelium is located at the interface between the host and environment and functions as the first line of defense against microorganisms, pollutants, and allergens [1, 2]
To investigate the effects of Aspergillus protease on inflammatory responses, the production of interleukin- (IL-) 1β; tumor necrosis factor- (TNF-) α; IL-8; regulated on activation, normal T cell expressed and secreted (RANTES); monocyte chemotactic protein- (MCP-) 1, eotaxin-1, and IL-6 was assessed in inactive protease- or Aspergillus protease-stimulated BEAS2B cells
The inhibitory effects of glycyrrhetinic acid (GA) on Aspergillus proteasemediated mitochondrial reactive oxygen species (ROS) production were diminished in uncoupling protein-2 (UCP-2)-knockdown cells (Figure 5(c)). These results suggest that the inhibitory function of GA against Aspergillus protease-induced mitochondrial ROS production is mediated by UCP-2

Summary

Introduction

The airway epithelium is located at the interface between the host and environment and functions as the first line of defense against microorganisms, pollutants, and allergens [1, 2]. The physical barrier function of the airway epithelium depends on cellular integrity which is sustained by tight junction molecules. Various stimuli including potent allergens disrupt cellular integrity by cleaving the tight junction through their intrinsic enzymatic activity [3]. Fungi, house dust mites, and/or pollen-originated allergens induce the secretion of other proteases and activate pattern recognition receptors (PRRs) in the airway epithelium. These activated PRRs, such as Toll-like receptor and proteaseactivated receptors, induce signaling cascades involved in immune responses [4]. The airway epithelium acts as a physical barrier and plays a key role in controlling airway inflammation [5,6,7,8]

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