PI3Kgamma inhibition blocks glomerulonephritis and extends lifespan in a mouse model of systemic lupus.
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-lpr mouse model of SLE. Treatment reduced glomerulonephritis and prolonged lifespan, suggesting that P13Kgamma may be a useful target in the treatment of chronic inflammation.
Barber
Domingo F
DF
Department of Immunology and Oncology, and Animal Facility, Centro Nacional de Biotecnología/CSIC, Universidad Autónoma de Madrid, Cantoblanco, Madrid E-28049, Spain.
Bartolomé
Almira
A
Hernandez
Carmen
C
Flores
Juana M
JM
Redondo
Clara
C
Fernandez-Arias
Cristina
C
Camps
Montserrat
M
Rückle
Thomas
T
Schwarz
Matthias K
MK
Rodríguez
Santiago
S
Martinez-A
Carlos
C
Balomenos
Dimitrios
D
Rommel
Christian
C
Carrera
Ana C
AC
D000818:Animals; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D005260:Female; D008180:Lupus Erythematosus, Systemic / Q000188:drug therapy*; D008181:Lupus Nephritis / Q000517:prevention & control*; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011810:Quinoxalines / Q000494:pharmacology*; D045162:Thiazolidinediones / Q000494:pharmacology*
C505144:5-quinoxalin-6-ylmethylenethiazolidine-2,4-dione; D004791:Enzyme Inhibitors; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011810:Quinoxalines; D045162:Thiazolidinediones