title: PI3Kgamma inhibition blocks glomerulonephritis and extends lifespan in a mouse model of systemic lupus.
abstract: 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.
authors.affiliation: Department of Immunology and Oncology, and Animal Facility, Centro Nacional de Biotecnología/CSIC, Universidad Autónoma de Madrid, Cantoblanco, Madrid E-28049, Spain.
authors.forename: Domingo F
authors.initials: DF
authors.lastname: Barber
authors.forename: Almira
authors.initials: A
authors.lastname: Bartolomé
authors.forename: Carmen
authors.initials: C
authors.lastname: Hernandez
authors.forename: Juana M
authors.initials: JM
authors.lastname: Flores
authors.forename: Clara
authors.initials: C
authors.lastname: Redondo
authors.forename: Cristina
authors.initials: C
authors.lastname: Fernandez-Arias
authors.forename: Montserrat
authors.initials: M
authors.lastname: Camps
authors.forename: Thomas
authors.initials: T
authors.lastname: Rückle
authors.forename: Matthias K
authors.initials: MK
authors.lastname: Schwarz
authors.forename: Santiago
authors.initials: S
authors.lastname: Rodríguez
authors.forename: Carlos
authors.initials: C
authors.lastname: Martinez-A
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Balomenos
authors.forename: Christian
authors.initials: C
authors.lastname: Rommel
authors.forename: Ana C
authors.initials: AC
authors.lastname: Carrera
mesh_terms: 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*
chemical_list: C505144:5-quinoxalin-6-ylmethylenethiazolidine-2,4-dione; D004791:Enzyme Inhibitors; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011810:Quinoxalines; D045162:Thiazolidinediones