title: Mitochondrial uncoupling protein 2 protects splenocytes from oxidative stress-induced apoptosis during pathogen activation.
abstract: Accumulating evidences suggested that mitochondrial uncoupling protein 2 (UCP2) is involved in host defense in parasite infection, inflammation, and autoimmune responses. However, it remains unknown whether UCP2 is participated in the modulation of humoral immune response. Here we used quantitative PCR, ELISA, TUNEL assay, flow cytometry, etc. to study the role of UCP2 in spleen B lymphocytes during pathogen activation and obtained following results. First, UCP2 is highly expressed in splenocytes and its expression level in splenocytes is rapidly increased when the cells are activated by lipopolysaccharide (LPS) in vivo or by LPS plus cytokines in vitro. Second, in contrast to the wild type (WT) littermates, the UCP2 knockout (UCP2-KO) mice show an impaired humoral immune response when they are challenged by pathogen. Although UCP2-KO mice produce a normal level of IgM, the levels of IgGs are significantly less than those of WT littermates. Third, splenocytes from UCP2-KO mice are more susceptible to pathogen activation-induced apoptosis, and the high level of reactive oxygen species (ROS) in UCP2-KO mice may be the cause for the apoptosis. In conclusion, our study demonstrates that mitochondrial UCP2 plays a critical role in protecting splenocytes from oxidative stress-induced apoptosis during pathogen activation.
authors.affiliation: Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Jiangsu 210093, China; Marine Biology Lab, School of Life Sciences, Nanjing University, Jiangsu 210093, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Cao
authors.affiliation: Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Jiangsu 210093, China.
authors.forename: Yeyan
authors.initials: Y
authors.lastname: Dong
authors.affiliation: Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Jiangsu 210093, China; Marine Biology Lab, School of Life Sciences, Nanjing University, Jiangsu 210093, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Tang
authors.affiliation: Marine Biology Lab, School of Life Sciences, Nanjing University, Jiangsu 210093, China.
authors.forename: Junyuan
authors.initials: J
authors.lastname: Chen
authors.affiliation: Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Jiangsu 210093, China.
authors.forename: Chen-Yu
authors.initials: CY
authors.lastname: Zhang
authors.affiliation: Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Jiangsu 210093, China. Electronic address: kekezen@163.com.
authors.forename: Ke
authors.initials: K
authors.lastname: Zen
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D016207:Cytokines / Q000096:biosynthesis / Q000494:pharmacology; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D005786:Gene Expression Regulation / Q000187:drug effects; D007113:Immunity, Innate / Q000187:drug effects; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000276:immunology; D007075:Immunoglobulin M / Q000096:biosynthesis / Q000276:immunology; D007473:Ion Channels / Q000235:genetics / Q000276:immunology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008214:Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D008264:Macrophages / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008928:Mitochondria / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000235:genetics / Q000276:immunology*; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000819:agonists / Q000276:immunology; D013154:Spleen / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D000071246:Uncoupling Protein 2
chemical_list: D016207:Cytokines; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D007473:Ion Channels; D008070:Lipopolysaccharides; D024101:Mitochondrial Proteins; D017382:Reactive Oxygen Species; C000604390:Ucp2 protein, mouse; D000071246:Uncoupling Protein 2
keywords: Immune response; Pathogen activation; Reactive oxygen species; Uncoupling protein 2