PI3Kγ inhibition blocks glomerulonephritis and extends lifespan in a mouse model of systemic lupus

被引：268

作者：

Barber, DF

Bartolomé, A

Hernandez, C

Flores, JM

Redondo, C

Fernandez-Arias, C

Camps, M

Ruckle, T

Schwarz, MK

Rodríguez, S

Martinez-A, C

Balomenos, D

Rommel, C

Carrera, AC ^{[1
]}

机构：

[1] Univ Autonoma Madrid, Dept Immunol & Oncol, CSIC, Ctr Nacl Biotecnol, E-28049 Madrid, Spain

[2] Univ Autonoma Madrid, Anim Facil, CSIC, Ctr Nacl Biotecnol, E-28049 Madrid, Spain

[3] Univ Complutense Madrid, Sch Vet, Dept Anim Med & Surg, E-28040 Madrid, Spain

[4] Hosp Ramon & Cajal, E-28034 Madrid, Spain

[5] Serono Int SA, Serono Pharmaceut Res Inst, CH-1211 Geneva, Switzerland

来源：

NATURE MEDICINE | 2005年 / 11卷 / 09期

关键词：

D O I：

10.1038/nm1291

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Systemic lupus erythematosus (SLE) is a chronic inflammatory disease generated by deregulation of T cell - mediated B- cell activation, which results in glomerulonephritis and renal failure. Disease is treated with immunosuppressants and cytostatic agents that have numerous side effects. Here we examine the use of inhibitors of phosphoinositide 3- kinase (PI3K) gamma, a lipid kinase that regulates inflammation, in the MRL- Ipr mouse model of SLE. Treatment reduced glomerulonephritis and prolonged lifespan, suggesting that PI3K gamma may be a useful target in the treatment of chronic inflammation.

引用

页码：933 / 935

页数：3

共 15 条

[1] Blockade of PI3Kγ suppresses joint inflammation and damage in mouse models of rheumatoid arthritis
Camps, M
Rückle, T
Ji, H
Ardissone, V
Rintelen, F
Shaw, J
Ferrandi, C
Chabert, C
Gillieron, C
Françon, B
Martin, T
Gretener, D
Perrin, D
Leroy, D
Vitte, PA
Hirsch, E
Wymann, MP
Cirillo, R
Schwarz, MK
Rommel, C
[J]. NATURE MEDICINE, 2005, 11 (09) : 936 - 943
[2] Cervera R., 2003, J Rheumatol, V6, P150, DOI [10.1046/j.0219-0494.2003.00039.x, DOI 10.1046/J.0219-0494.2003.00039.X]
[3] Treatment of lupus with corticosteroids
Chatham, WW
Kimberly, RP
[J]. LUPUS, 2001, 10 (03) : 140 - 147
[4] Dai CS, 2001, CHINESE MED J-PEKING, V114, P864
[5] Central role for G protein-coupled phosphoinositide 3-kinase γ in inflammation
Hirsch, E
Katanaev, VL
Garlanda, C
Azzolino, O
Pirola, L
Silengo, L
Sozzani, S
Mantovani, A
Altruda, F
Wymann, MP
[J]. SCIENCE, 2000, 287 (5455) : 1049 - 1053
[6] INGHIRAMI G, 1988, CLIN EXP RHEUMATOL, V6, P269
[7] PREVENTION OF NEPHRITIS IN MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-II-DEFICIENT MRL-LPR MICE
JEVNIKAR, AM
GRUSBY, MJ
GLIMCHER, LH
[J]. JOURNAL OF EXPERIMENTAL MEDICINE, 1994, 179 (04) : 1137 - 1143
[8] Increased severity of murine lupus in female mice is due to enhanced expansion of pathogenic T cells
Lang, TJ
Nguyen, P
Papadimitriou, JC
Via, CS
[J]. JOURNAL OF IMMUNOLOGY, 2003, 171 (11) : 5795 - 5801
[9] Neidhart M, 1996, SCHWEIZ MED WSCHR, V126, P1922
[10] Pathogenic T cells in murine lupus exhibit spontaneous signaling activity through phosphatidylinositol 3-kinase and mitogen-activated protein kinase pathways
Niculescu, F
Nguyen, P
Niculescu, T
Rus, H
Rus, V
Via, CS
[J]. ARTHRITIS AND RHEUMATISM, 2003, 48 (04): : 1071 - +

← 1 2 →