PI3Kgamma inhibition blocks glomerulonephritis and extends lifespan in a mouse model of systemic lupus

Nat Med. 2005 Sep;11(9):933-5. doi: 10.1038/nm1291. Epub 2005 Aug 28.

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.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Disease Models, Animal
  • Enzyme Inhibitors / therapeutic use*
  • Female
  • Lupus Erythematosus, Systemic / drug therapy*
  • Lupus Nephritis / prevention & control*
  • Male
  • Mice
  • Mice, Mutant Strains
  • Phosphoinositide-3 Kinase Inhibitors*
  • Quinoxalines / pharmacology*
  • Thiazolidinediones / pharmacology*

Substances

  • 5-quinoxalin-6-ylmethylenethiazolidine-2,4-dione
  • Enzyme Inhibitors
  • Phosphoinositide-3 Kinase Inhibitors
  • Quinoxalines
  • Thiazolidinediones