title: Doxycycline Induces Mitophagy and Suppresses Production of Interferon-β in IPEC-J2 Cells.
abstract: Previous reports have demonstrated that the second-generation tetracycline derivative doxycycline (DOX) interrupts mitochondrial proteostasis and physiology, inhibits proliferation of many cell types, and induces apoptosis. However, the effects of DOX, which is widely used in porcine husbandry by feed, on the porcine intestinal epithelium are unclear. In this study, we demonstrated that DOX damaged mitochondrial morphology and induced the co-localization of mitochondria with autophagosomes, suggesting that DOX induces mitophagy in IPEC-J2 cells. We also found evidence that DOX increased intracellular levels of reactive oxygen species (ROS) or mitochondrial-specific ROS in a dose dependent manner. Moreover, 50 μg/ml DOX significantly decreased production of interferon-β and facilitated replication of transmissible gastroenteritis coronavirus in IPEC-J2 cells. These results demonstrated that DOX induced mitophagy and ROS production, which damaged the intestinal epithelium. As DOX is used extensively in pig husbandry, uncontrolled application poses a significant threat of viral infection, so stricter policies on its usage should be required.
authors.affiliation: Key Laboratory of Animal Physiology and Biochemistry, Ministry of Agriculture, Nanjing Agricultural University Nanjing, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Xing
authors.affiliation: Key Laboratory of Animal Physiology and Biochemistry, Ministry of Agriculture, Nanjing Agricultural University Nanjing, China.
authors.forename: Zhu
authors.initials: Z
authors.lastname: Liqi
authors.affiliation: Department of Zoology, College of Life Sciences, Nanjing Agricultural University Nanjing, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Jian
authors.affiliation: Key Laboratory of Animal Physiology and Biochemistry, Ministry of Agriculture, Nanjing Agricultural University Nanjing, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Qinghua
authors.affiliation: Key Laboratory of Animal Physiology and Biochemistry, Ministry of Agriculture, Nanjing Agricultural University Nanjing, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Qian
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001343:Autophagy / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004318:Doxycycline / Q000494:pharmacology*; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism / Q000821:virology; D007113:Immunity, Innate / Q000187:drug effects; D016899:Interferon-beta / Q000096:biosynthesis*; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism / Q000821:virology; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D063306:Mitophagy / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000378:metabolism; D013552:Swine; D005760:Transmissible gastroenteritis virus / Q000502:physiology; D014779:Virus Replication
chemical_list: D017382:Reactive Oxygen Species; D016899:Interferon-beta; D004318:Doxycycline
keywords: IFN-β; IPEC-J2 cells; TGEV; doxycycline; mitophagy