Monocytes are resistant to apoptosis in systemic juvenile idiopathic arthritis.
We investigated whether circulating monocytes from patients with systemic juvenile idiopathic arthritis (SJIA) are resistant to apoptosis and which apoptotic pathway(s) may mediate this resistance. A microarray analysis of peripheral blood mononuclear cells (PBMC) of SJIA samples and RT-PCR analysis of isolated monocytes showed that monocytes from active SJIA patients express transcripts that imply resistance to apoptosis. SJIA monocytes incubated in low serum show reduced annexin binding and diminished FasL up-regulation compared to controls. SJIA monocytes are less susceptible to anti-Fas-induced apoptosis and, upon activation of the mitochondrial pathway with staurosporine, show diminished Bid cleavage and Bcl-w down-regulation compared to controls. Exposure to SJIA plasma reduces responses to apoptotic triggers in normal monocytes. Thus, SJIA monocytes are resistant to apoptosis due to alterations in both the extrinsic and intrinsic apoptosis pathways, and circulating factors associated with active SJIA may confer this phenotype.
Srivastava
Shivani
S
Department of Biology, Stanford University, Stanford, CA, USA.
Macaubas
Claudia
C
Deshpande
Chetan
C
Alexander
Heather C
HC
Chang
Sheng-Yung
SY
Sun
Yue
Y
Park
Jane L
JL
Lee
Tzielan
T
Begovich
Ann
A
Mellins
Elizabeth D
ED
D000293:Adolescent; D000906:Antibodies / Q000276:immunology; D017209:Apoptosis / Q000235:genetics / Q000502:physiology*; D001171:Arthritis, Juvenile / Q000097:blood / Q000503:physiopathology*; D002470:Cell Survival; D002478:Cells, Cultured; D002648:Child; D053222:Fas Ligand Protein / Q000378:metabolism; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D008928:Mitochondria / Q000378:metabolism; D009000:Monocytes / Q000166:cytology / Q000502:physiology*; D019014:fas Receptor / Q000276:immunology
D000906:Antibodies; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D019014:fas Receptor
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