House dust mite allergen Der f 1 induces IL-8 in human basophilic cells via ROS-ERK and p38 signal pathways |
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| Institution: | 1. Department of Environmental Medical Biology and Arthropods of Medical Importance Resource Bank, Institute of Tropical Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea;2. Brain Korea 21 PLUS Project for Medical Science, Yonsei University, Seoul, Republic of Korea;3. Department of Internal Medicine, Institute of Allergy, Yonsei University College of Medicine, Seoul, Republic of Korea;4. Department of Microbiology, Ajou University School of Medicine, Suwon 443-721, Republic of Korea;1. College of Pharmacy, Xi’an Jiaotong University, Xi''an 710061, China;2. Department of Anesthesiology, Xi''an Honghui Hospital, Xi''an Jiaotong University, Xi''an 710054, China;1. Institute for Infection and Immunity, St George''s, University of London, London, United Kingdom;2. Faculty of Life Sciences, University of Manchester, Manchester, United Kingdom;1. Department of Pharmacology, Kangwon National University School of Medicine, Chuncheon, 24341, South Korea;2. Department of Medical Environmental Biology and Tropical Medicine, Kangwon National University School of Medicine, Chuncheon, 24341, South Korea;3. Department of Physiology, Kangwon National University School of Medicine, Chuncheon, 24341, South Korea;4. College of Pharmacy, Kangwon National University, Chuncheon, 24341, South Korea |
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| Abstract: | Der f 1, a major house dust mite allergen and member of the papain-like cysteine protease family, can provoke immune responses with its proteolytic activity. To understand the role of Der f 1 in inflammatory immune responses, we studied the mechanism of the regulation of interleukin (IL)-8 expressions in human basophilic cell KU812 by proteolytically active recombinant Der f 1. Not only production of IL-8 mRNA was induced but also the DNA binding activity of activator protein-1 (AP-1) and phosphorylation of NF-κB p65 were increased in Der f 1-treated KU812. Furthermore, Der f 1 induction of IL-8 expression was sensitive to pharmacological inhibition of ERK and p38 mitogen activated protein kinase (MAPK) pathways. Der f 1 also activated ERK and p38 MAPK phosphorylation and rapidly induced reactive oxygen species (ROS) production. The antioxidant N-acetyl-cysteine (NAC) inhibited phosphorylation of ERK, but not p38, suggesting that secretion of IL-8 in KU812 cells treated with Der f 1 is dependent on ROS, ERK MAPK and p38 MAPK. We describe the mechanism of Der f 1-induced IL-8 secretion from human basophilic cells, which are thought to be important for allergic inflammation independent of IgE antibodies. These findings improve our understanding of the inflammatory immune response in human basophils to protease allergens. |
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| Keywords: | Basophil KU812 Cysteine protease Der f 1 IL-8 |
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