Mitochondrial reactive oxygen species regulate fungal protease-induced inflammatory responses

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• 作者：Yun Hee Kim^a ; ^b ; Seung-Hyo Lee^a ; ^{sl131345@kaist.ac.kr}
• 关键词：Aspergillus protease ; Mitochondrial ROS ; Airway epithelium ; Inflammation ; MAP kinase ; AP-1
• 刊名：Toxicology
• 出版年：2017
• 出版时间：1 March 2017
• 年：2017
• 卷：378
• 期：Complete
• 页码：86-94
• 全文大小：1051 K
• 卷排序：378

文摘

Epidemiological studies have shown that fungal infections are a main cause of respiratory tract diseases, such as asthma, bronchopneumonia, intoxication, and invasive fungal disease. Fungi such as Aspergillus and Candida species have become increasingly important pathogens as the global climate changes. Accordingly, in this study, we evaluated the toxicological potential of Aspergillus protease in the lower respiratory tract. Exposure of Aspergillus protease to A549 cells induced upregulation of tumor necrosis factor (TNF)-α, monocyte chemoattractant protein (MCP)-1, and intercellular adhesion molecule (ICAM)-1 mRNAs and increased production of interleukin (IL)-8 and MCP-1 protein through enhanced mitochondrial reactive oxygen species (ROS) generation and activation of mitogen-activated protein kinase (MAPK) and activator protein (AP)-1. Furthermore, the mitochondrial ROS scavenger Mito-TEMPO, which inhibited MAPK and AP-1, significantly reduced MCP-1 and IL-1β mRNA expression and reduced HL-60 cell migration through the suppression of MCP-1 and IL-8 protein secretion. Thus, our results demonstrated that mitochondria were an important source of Aspergillus protease-stimulated ROS and that regulation of mitochondrial ROS modulated inflammatory responses by preventing activation of MAPK and AP-1 in A549 cells.