title: Investigation of the caspase-dependent mitochondrial apoptotic pathway in mononuclear cells of patients with systemic Lupus erythematosus.
abstract: BACKGROUND
  This study aimed to explore the role of apoptosis initiators, caspase-9, caspase-10, mitochondrial anti-viral signaling protein (MAVS), and interferon regulatory factor 7 (pIRF7), in patients with systemic lupus erythematosus (SLE).
  
  
  METHODS
  Leukocyte apoptosis was determined by flow cytometry, including annexin V, APO2.7, and 7-amino-actinomycin D (7-AAD) on each subtype of leukocyte in 35 patients with SLE, 15 disease controls, and 17 volunteer normal controls. Levels of caspase-9, caspase-10, MAVS, and pIRF7 in mononuclear cells and the disease activity index (SLEDAI) in the SLE patients were determined. Correlation among intracellular adaptor proteins and caspase levels were calculated.
  
  
  RESULTS
  The SLE patients had higher APO2.7 in total leukocyte, lymphocyte, and monocytes, and higher late apoptosis markers in total leukocytes and neutrophils than normal controls (all p < 0.05). Disease activity was positively associated with the APO2.7 of CD19+ cells in SLE, but negatively associated with MAVS and caspase-9 levels (all p < 0.05). Markers of viral infection and anti-virus transcription factors like MDA5, MAVS, and pIRF7 were significantly higher in SLE patients than in disease controls (p < 0.05). Caspase-9 and caspase-10 levels positively correlated with MAVS and pIRF7 in SLE patients (p < 0.05).
  
  
  CONCLUSIONS
  The disease activity of SLE is positively associated with APO2.7 level of CD19+ cells but negatively associated with MAVS and caspase-9 levels, which all point to a mitochondrial pathway.
authors.affiliation: Department of Biological Science, National Sun Yat-Sen University, Kaohsiung, Taiwan. bensu8@gmail.com.|Departments of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan. bensu8@gmail.com.
authors.forename: Yu-Jih
authors.initials: YJ
authors.lastname: Su
authors.affiliation: Departments of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan. tiantsai@ms2.hinet.net.
authors.forename: Tien-Tsai
authors.initials: TT
authors.lastname: Cheng
authors.affiliation: Departments of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan. chungjencgmh@gmail.com.
authors.forename: Chung-Jen
authors.initials: CJ
authors.lastname: Chen
authors.affiliation: Departments of Neurology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan. cwenneng@ms19.hinet.net.
authors.forename: Wen-Neng
authors.initials: WN
authors.lastname: Chang
authors.affiliation: Departments of Neurology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan. naiwen@adm.cgmh.org.tw.
authors.forename: Nai-Wen
authors.initials: NW
authors.lastname: Tsai
authors.affiliation: Departments of Emergency Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan. kungchiate@gmail.com.
authors.forename: Chia-Te
authors.initials: CT
authors.lastname: Kung
authors.affiliation: Departments of Neurosurgery, and Radiology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan. m82whc@yahoo.com.tw.
authors.forename: Hung-Chen
authors.initials: HC
authors.lastname: Wang
authors.affiliation: Departments of Radiology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan. u64lin@yahoo.com.tw.
authors.forename: Wei-Che
authors.initials: WC
authors.lastname: Lin
authors.affiliation: Departments of Neurology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan. hjc2828@gmail.com.
authors.forename: Chih-Cheng
authors.initials: CC
authors.lastname: Huang
authors.affiliation: Department of Biological Science, National Sun Yat-Sen University, Kaohsiung, Taiwan. emily0606@cgmh.org.tw.|Departments of Neurology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan. emily0606@cgmh.org.tw.
authors.forename: Ya-Ting
authors.initials: YT
authors.lastname: Chang
authors.affiliation: Department of Biological Science, National Sun Yat-Sen University, Kaohsiung, Taiwan. mitosu@gmail.com.|Departments of Emergency Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan. mitosu@gmail.com.
authors.forename: Chih-Min
authors.initials: CM
authors.lastname: Su
authors.affiliation: Departments of Neurology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan. ifmaymay@gmail.com.
authors.forename: Yi-Fang
authors.initials: YF
authors.lastname: Chiang
authors.affiliation: Department of Biological Science, National Sun Yat-Sen University, Kaohsiung, Taiwan. benzmcl@yahoo.com.tw.|Departments of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan. benzmcl@yahoo.com.tw.
authors.forename: Ben-Chung
authors.initials: BC
authors.lastname: Cheng
authors.affiliation: Department of Biological Science, National Sun Yat-Sen University, Kaohsiung, Taiwan. lyr1022@adm.cgmh.org.tw.|Departments of Neurosurgery, and Radiology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan. lyr1022@adm.cgmh.org.tw.
authors.forename: Yu-Jun
authors.initials: YJ
authors.lastname: Lin
authors.affiliation: Department of Biological Science, National Sun Yat-Sen University, Kaohsiung, Taiwan. chlu99@ms44.url.com.tw.|Departments of Neurology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan. chlu99@ms44.url.com.tw.|Department of Neurology, Chang Gung Memorial Hospital, 123, Ta Pei Road, Niao Sung Hsiang, Kaohsiung, Taiwan. chlu99@ms44.url.com.tw.
authors.forename: Cheng-Hsien
authors.initials: CH
authors.lastname: Lu
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000328:Adult; D017209:Apoptosis; D015415:Biomarkers / Q000378:metabolism; D016022:Case-Control Studies; D053455:Caspase 10 / Q000378:metabolism*; D053453:Caspase 9 / Q000378:metabolism*; D003710:Demography; D005260:Female; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D008180:Lupus Erythematosus, Systemic / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology*; D008214:Lymphocytes / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000378:metabolism*; D009000:Monocytes / Q000378:metabolism / Q000473:pathology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D015415:Biomarkers; C505371:MAVS protein, human; D053455:Caspase 10; D053453:Caspase 9; C506438:CASP10 protein, human