| Content Provider |
World Health Organization (WHO)-Global Index Medicus |
| Author |
Suárez-Fueyo, Abel Steiner, Bart H. García, Esther Carrera, Ana C. Barber, Domingo F. Puri, Kamal D. Rojas, José M. Cariaga, Ariel E. |
| Description |
Author Affiliation: Suárez-Fueyo A ( Departamento de Inmunología y Oncología, Centro Nacional de Biotecnología/Consejo Superior de Investigaciones Científicas, Cantoblanco, Madrid 28049, Spain); Rojas JM ( Departamento de Inmunología y Oncología, Centro Nacional de Biotecnología/Consejo Superior de Investigaciones Científicas, Cantoblanco, Madrid 28049, Spain); Cariaga AE ( Departamento de Inmunología y Oncología, Centro Nacional de Biotecnología/Consejo Superior de Investigaciones Científicas, Cantoblanco, Madrid 28049, Spain); García E ( Departamento de Biologia Molecular e Celular, Centro Nacional de Biotecnología/Consejo Superior de Investigaciones Científicas, Cantoblanco, Madrid 28049, Spain); Steiner BH ( Department of Biology, Gilead Sciences, Seattle, WA 98102.); Barber DF ( Departamento de Inmunología y Oncología, Centro Nacional de Biotecnología/Consejo Superior de Investigaciones Científicas, Cantoblanco, Madrid 28049, Spain); Puri KD ( Department of Biology, Gilead Sciences, Seattle, WA 98102.); Carrera AC ( Departamento de Inmunología y Oncología, Centro Nacional de Biotecnología/Consejo Superior de Investigaciones Científicas, Cantoblanco, Madrid 28049, Spain) |
| Abstract |
Systemic lupus erythematosus (SLE) is a human chronic inflammatory disease generated and maintained throughout life by autoreactive T and B cells. Class I phosphoinositide 3-kinases (PI3K) are heterodimers composed of a regulatory and a catalytic subunit that catalyze phosphoinositide-3,4,5-P3 formation and regulate cell survival, migration, and division. Activity of the PI3Kδ isoform is enhanced in human SLE patient PBLs. In this study, we analyzed the effect of inhibiting PI3Kδ in MRL/lpr mice, a model of human SLE. We found that PI3Kδ inhibition ameliorated lupus progression. Treatment of these mice with a PI3Kδ inhibitor reduced the excessive numbers of CD4(+) effector/memory cells and B cells. In addition, this treatment reduced serum TNF- levels and the number of macrophages infiltrating the kidney. Expression of inactive PI3Kδ, but not deletion of the other hematopoietic isoform PI3Kγ, reduced the ability of macrophages to cross the basement membrane, a process required to infiltrate the kidney, explaining MRL/lpr mice improvement by pharmacologic inhibition of PI3Kδ. The observations that p110δ inhibitor prolonged mouse life span, reduced disease symptoms, and showed no obvious secondary effects indicates that PI3Kδ is a promising target for SLE. |
| ISSN |
00221767 |
| e-ISSN |
15506606 |
| Journal |
The Journal of Immunology |
| Issue Number |
2 |
| Volume Number |
193 |
| Language |
English |
| Publisher |
The American Association of Immunologists |
| Publisher Date |
2014-07-15 |
| Publisher Place |
United States |
| Access Restriction |
Open |
| Subject Keyword |
Adenosine Analogs & Derivatives Kidney Drug Effects Lupus Erythematosus, Systemic Prevention & Control Macrophages Phosphatidylinositol 3-kinases Antagonists & Inhibitors Protein Kinase Inhibitors Pharmacology Quinazolinones Chemistry Animals Antibodies, Antinuclear Blood Cd4-positive T-lymphocytes Metabolism Pathology Cd8-positive T-lymphocytes Cells, Cultured Class Ib Phosphatidylinositol 3-kinase Cytokines Dose-response Relationship, Drug Flow Cytometry Immunoglobulin G Lupus Nephritis Lymphocyte Count Mice Mice, Inbred C57bl Mice, Inbred Mrl Lpr Microscopy, Confocal Molecular Structure Quinoxalines Survival Analysis Thiazolidinediones Research Support, Non-u.s. Gov't Discipline Immunology |
| Content Type |
Text |
| Resource Type |
Article |
| Subject |
Immunology and Allergy Immunology |
