The Role of Reactive Oxygen Species (ROS) in the Expression of Endothelial Adhesion Molecules in Allergic Inflammation

Abstract

In the pathogenesis of allergic diseases, such as atopic dermatitis, the expressions of adhesion molecules and subsequent adhesion of inflammatory cells to endothelial cells are necessary. It is known that reactive oxygen species(ROS) are important second messengers in this process. We studied the effect of allergic reaction-related cytokines on the production of ROS as well as the role of ROS in the expressions of adhesion molecules in the human dermal microvascular endothelial cells(HDMECs). The generation and expressions of ROS and adhesion molecules were determined by FACstar and ELISA, respectively after stimulations with H2O2, IL-1α, TNF-α, IL-4, IL-13, and H2O2 combined with cytokines and cytokines combined with antioxidants. The results are: 1)Stimulations of HDMECs with IL-1α, TNF-α, IL-4 and IL-13 increased production of ROS at early time points from 15 min to 30 min after incubation. The expressions of ICAM-1, VCAM-1 and E-selectin were upregulated or induced by IL-1α and TNF-α while the expression of VCAM-1 was induced by IL-4, IL-13. 2)The stimulation of HDMECs with H2O2 upregulated or induced the expressions of ICAM-1, VCAM-1 and E-selectin but no synergistic or additive effect was found between cytokines and H2O2. 3)The expressions of the adhesion molecules upregulated or induced by cytokines were variably inhibited by antioxidants. These findings suggest that ROS play an important role in the expressions of the ICAM-1, VCAM-1 and E-selectin induced by allergic reaction-related cytokines and that pharmaceutical approaches manipulating reduction-oxidation mechanism could lead to a new therapeutic approach for allergic diseases.