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Investigation of the caspase-dependent mitochondrial apoptotic pathway in mononuclear cells of patients with systemic lupus erythematosus.

Su YJ, Cheng TT, Chen CJ, Chang WN, Tsai NW, Kung CT, Wang HC, Lin WC, Huang CC, Chang YT, Su CM, Chiang YF, Cheng BC, Lin YJ, Lu CH - J Transl Med (2014)

Bottom Line: 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).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.

View Article: PubMed Central - PubMed

Affiliation: Department of Biological Science, National Sun Yat-Sen University, Kaohsiung, Taiwan. bensu8@gmail.com.

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.

No MeSH data available.


Related in: MedlinePlus

Correlation between MAVS and SLEDAI. (a) Origin correlation between MAVS and SLEDAI. (b) Correlation between MAVS and SLEDAI after eliminating the low-MDA5 sub-group.
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Fig4: Correlation between MAVS and SLEDAI. (a) Origin correlation between MAVS and SLEDAI. (b) Correlation between MAVS and SLEDAI after eliminating the low-MDA5 sub-group.

Mentions: The negative coefficient between MAVS and SLE disease activity (Table 3) was enhanced if patients with lower MDA5 levels (cut-off value, 366 pg/mL, mean of disease controls) were removed (Figure 4). The p value changed from 0.04955 to 0.01123, indicating that SLE was a heterogeneous group and could be divided into at least two subgroups according to MDA5 levels. Disease activity negatively correlated with MAVS in the high MDA5 level SLE patients (p < 0.05) but not in the low MDA5 level SLE patients (p = 0.67) (data not shown).Figure 4


Investigation of the caspase-dependent mitochondrial apoptotic pathway in mononuclear cells of patients with systemic lupus erythematosus.

Su YJ, Cheng TT, Chen CJ, Chang WN, Tsai NW, Kung CT, Wang HC, Lin WC, Huang CC, Chang YT, Su CM, Chiang YF, Cheng BC, Lin YJ, Lu CH - J Transl Med (2014)

Correlation between MAVS and SLEDAI. (a) Origin correlation between MAVS and SLEDAI. (b) Correlation between MAVS and SLEDAI after eliminating the low-MDA5 sub-group.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4226892&req=5

Fig4: Correlation between MAVS and SLEDAI. (a) Origin correlation between MAVS and SLEDAI. (b) Correlation between MAVS and SLEDAI after eliminating the low-MDA5 sub-group.
Mentions: The negative coefficient between MAVS and SLE disease activity (Table 3) was enhanced if patients with lower MDA5 levels (cut-off value, 366 pg/mL, mean of disease controls) were removed (Figure 4). The p value changed from 0.04955 to 0.01123, indicating that SLE was a heterogeneous group and could be divided into at least two subgroups according to MDA5 levels. Disease activity negatively correlated with MAVS in the high MDA5 level SLE patients (p < 0.05) but not in the low MDA5 level SLE patients (p = 0.67) (data not shown).Figure 4

Bottom Line: 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).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.

View Article: PubMed Central - PubMed

Affiliation: Department of Biological Science, National Sun Yat-Sen University, Kaohsiung, Taiwan. bensu8@gmail.com.

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.

No MeSH data available.


Related in: MedlinePlus