title: Mitochondrial reactive oxygen species regulate fungal protease-induced inflammatory responses.
abstract: 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.
authors.affiliation: Graduate School of Medical Science and Engineering, Biomedical Research Center, KAIST Institute for the BioCentury, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Republic of Korea; Korean Medicine Convergence Research Division, Korea Institute of Oriental Medicine (KIOM), Daejeon 34054, Republic of Korea.
authors.forename: Yun Hee
authors.initials: YH
authors.lastname: Kim
authors.affiliation: Graduate School of Medical Science and Engineering, Biomedical Research Center, KAIST Institute for the BioCentury, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Republic of Korea. Electronic address: sl131345@kaist.ac.kr.
authors.forename: Seung-Hyo
authors.initials: SH
authors.lastname: Lee
mesh_terms: D000072283:A549 Cells; D001230:Aspergillus; D002465:Cell Movement; D002470:Cell Survival; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D005656:Fungal Proteins / Q000378:metabolism*; D018922:HL-60 Cells; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D010447:Peptide Hydrolases / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D018808:Transcription Factor AP-1 / Q000378:metabolism
chemical_list: D016207:Cytokines; D005656:Fungal Proteins; D017382:Reactive Oxygen Species; D018808:Transcription Factor AP-1; D018799:Intercellular Adhesion Molecule-1; D020928:Mitogen-Activated Protein Kinases; D010447:Peptide Hydrolases
keywords: AP-1; Airway epithelium; Aspergillus protease; Inflammation; MAP kinase; Mitochondrial ROS