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: Yu-Jih Su, Tien-Tsai Cheng, Chung-Jen Chen, Wen-Neng Chang, Nai-Wen Tsai, Chia-Te Kung, Hung-Chen Wang, Wei-Che Lin, Chih-Cheng Huang, Ya-Ting Chang, Chih-Min Su, Yi-Fang Chiang, Ben-Chung Cheng, Yu-Jun Lin, Cheng-Hsien Lu
• Journal: Journal of translational medicine (J Transl Med) Vol. 12 Pg. 303 (Nov 06 2014) ISSN: 1479-5876 [Electronic] England
• PMID: 25370148 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Adaptor Proteins, Signal Transducing
• Biomarkers
• MAVS protein, human
• Caspase 10
• Caspase 9
• CASP10 protein, human

Topics

• Adaptor Proteins, Signal Transducing (metabolism)
• Adult
• Apoptosis
• Biomarkers (metabolism)
• Case-Control Studies
• Caspase 10 (metabolism)
• Caspase 9 (metabolism)
• Demography
• Female
• Humans
• Leukocytes, Mononuclear (enzymology, metabolism, pathology)
• Lupus Erythematosus, Systemic (enzymology, metabolism, pathology)
• Lymphocytes (metabolism, pathology)
• Male
• Middle Aged
• Mitochondria (metabolism)
• Monocytes (metabolism, pathology)