title: Monocytes are resistant to apoptosis in systemic juvenile idiopathic arthritis.
abstract: 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.
authors.affiliation: Department of Biology, Stanford University, Stanford, CA, USA.
authors.forename: Shivani
authors.initials: S
authors.lastname: Srivastava
authors.forename: Claudia
authors.initials: C
authors.lastname: Macaubas
authors.forename: Chetan
authors.initials: C
authors.lastname: Deshpande
authors.forename: Heather C
authors.initials: HC
authors.lastname: Alexander
authors.forename: Sheng-Yung
authors.initials: SY
authors.lastname: Chang
authors.forename: Yue
authors.initials: Y
authors.lastname: Sun
authors.forename: Jane L
authors.initials: JL
authors.lastname: Park
authors.forename: Tzielan
authors.initials: T
authors.lastname: Lee
authors.forename: Ann
authors.initials: A
authors.lastname: Begovich
authors.forename: Elizabeth D
authors.initials: ED
authors.lastname: Mellins
mesh_terms: 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
chemical_list: D000906:Antibodies; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D019014:fas Receptor
references.citation: Proc Natl Acad Sci U S A. 2002 Jan 8;99(1):345-50
references.pmid: 11756671
references.citation: Ann Rheum Dis. 2003 Aug;62(8):761-3
references.pmid: 12860732
references.citation: Nature. 2000 Feb 3;403(6769):503-11
references.pmid: 10676951
references.citation: J Immunol. 2001 Nov 1;167(9):5404-11
references.pmid: 11673559
references.citation: Curr Opin Rheumatol. 2002 Sep;14(5):548-52
references.pmid: 12192253
references.citation: Eur J Immunol. 2001 Aug;31(8):2421-30
references.pmid: 11500826
references.citation: Arthritis Rheum. 2004 Dec;50(12):3762-71
references.pmid: 15593206
references.citation: J Immunol. 1991 Nov 15;147(10):3408-12
references.pmid: 1940344
references.citation: Diabetes. 2008 May;57(5):1284-92
references.pmid: 18252892
references.citation: Arthritis Rheum. 2001 Aug;44(8):1782-5
references.pmid: 11508429
references.citation: J Rheumatol. 2007 Apr;34(4):823-30
references.pmid: 17343316
references.citation: Arthritis Rheum. 2007 Nov;56(11):3793-804
references.pmid: 17968951
references.citation: Lupus. 2008 May;17(5):371-5
references.pmid: 18490410
references.citation: J Exp Med. 2005 May 2;201(9):1479-86
references.pmid: 15851489
references.citation: Trends Cell Biol. 1998 Sep;8(9):365-72
references.pmid: 9728398
references.citation: J Biol Chem. 2001 Jun 8;276(23):20633-40
references.pmid: 11279218
references.citation: Rheumatology (Oxford). 2003 Feb;42(2):375-9
references.pmid: 12595640
references.citation: Int J Biochem Cell Biol. 2007;39(3):497-504
references.pmid: 17074529
references.citation: Cell. 2007 Apr 20;129(2):423-33
references.pmid: 17448999
references.citation: Nature. 1999 Aug 26;400(6747):886-91
references.pmid: 10476969
references.citation: J Immunol. 1999 Aug 15;163(4):1755-62
references.pmid: 10438906
references.citation: J Invest Dermatol. 2007 Aug;127(8):1947-55
references.pmid: 17429435
references.citation: Arthritis Rheum. 2007 Mar;56(3):965-71
references.pmid: 17328073
references.citation: Arthritis Rheum. 2002 Jan;46(1):232-7
references.pmid: 11817596
references.citation: Arthritis Rheum. 1986 Feb;29(2):274-81
references.pmid: 3485433
references.citation: J Exp Med. 1997 Apr 21;185(8):1511-6
references.pmid: 9126933
references.citation: J Virol. 2008 Apr;82(7):3702-12
references.pmid: 18216116
references.citation: Clin Immunol. 2010 Feb;134(2):206-16
references.pmid: 19879195
references.citation: Biol Reprod. 2001 Feb;64(2):518-26
references.pmid: 11159354
references.citation: Baillieres Clin Rheumatol. 1998 May;12(2):245-71
references.pmid: 9890097
references.citation: Am J Respir Cell Mol Biol. 2003 Nov;29(5):545-51
references.pmid: 12748057
references.citation: Arthritis Rheum. 1995 Dec;38(12):1735-7
references.pmid: 8849344
references.citation: Int J Oncol. 2003 Jan;22(1):15-20
references.pmid: 12469180
references.citation: Cell Death Differ. 2002 May;9(5):574-80
references.pmid: 11973615
references.citation: Blood. 2007 May 1;109(9):3776-85
references.pmid: 17218381
references.citation: Arthritis Rheum. 1995 Feb;38(2):211-20
references.pmid: 7848311
references.citation: Biol Pharm Bull. 2008 Mar;31(3):386-90
references.pmid: 18310897
references.citation: Cell Death Differ. 2006 Jun;13(6):994-1002
references.pmid: 16543937
references.citation: Cancer Cell. 2006 May;9(5):351-65
references.pmid: 16697956
references.citation: Genes Immun. 2004 Aug;5(5):347-53
references.pmid: 15175644
references.citation: Am J Respir Cell Mol Biol. 2008 Apr;38(4):380-5
references.pmid: 18192503
references.citation: Proc Natl Acad Sci U S A. 2000 Feb 15;97(4):1707-12
references.pmid: 10677522
references.citation: Biochem Pharmacol. 2008 Dec 1;76(11):1533-43
references.pmid: 18765235
references.citation: Arthritis Rheum. 2004 Apr;50(4):1286-95
references.pmid: 15077313
references.citation: Clin Exp Allergy. 2007 Mar;37(3):323-30
references.pmid: 17359382
references.citation: J Rheumatol. 1986 Jun;13(3):598-603
references.pmid: 3090248
references.citation: Arthritis Rheum. 2008 Dec;58(12):3924-31
references.pmid: 19035478
references.citation: Cold Spring Harb Symp Quant Biol. 1999;64:71-8
references.pmid: 11232339
references.citation: Proc Natl Acad Sci U S A. 1998 Dec 8;95(25):14863-8
references.pmid: 9843981
references.citation: Arthritis Res Ther. 2005;7(1):R30-7
references.pmid: 15642140
references.citation: Infect Immun. 2004 May;72(5):2590-7
references.pmid: 15102767
references.citation: EMBO J. 1998 Mar 16;17(6):1675-87
references.pmid: 9501089
references.citation: Arthritis Rheum. 2003 May;48(5):1398-407
references.pmid: 12746913
references.citation: J Immunol. 1991 Mar 1;146(5):1541-6
references.pmid: 1993844
references.citation: Scand J Rheumatol. 2004;33(1):7-12
references.pmid: 15124936
references.citation: Apoptosis. 2009 Apr;14(4):447-54
references.pmid: 19199037
references.citation: Proc Natl Acad Sci U S A. 2001 Apr 24;98(9):5116-21
references.pmid: 11309499
references.citation: Proc Natl Acad Sci U S A. 1998 Nov 24;95(24):14308-13
references.pmid: 9826696
references.citation: J Immunol. 1996 May 1;156(9):3469-77
references.pmid: 8617975
references.citation: J Biol Chem. 2008 Jul 18;283(29):20383-96
references.pmid: 18502749
references.citation: Nat Rev Immunol. 2007 Apr;7(4):255-66
references.pmid: 17380156
references.citation: Exp Dermatol. 2005 Apr;14(4):259-65
references.pmid: 15810883
references.citation: J Pediatr. 1986 Mar;108(3):405-9
references.pmid: 3081699
references.citation: Pathobiology. 1999;67(5-6):291-3
references.pmid: 10725805