PI3K inhibition in inflammation: Toward tailored therapies for specific diseases.
In the past decade, the availability of genetically modified animals has enabled the discovery of interesting roles for phosphatidylinositol 3-kinase-gamma (PI3Kgamma) and -delta (PI3Kdelta) in different cell types orchestrating innate and adaptive immune responses. Therefore, these PI3K isoforms appear to be attractive drug targets for the treatment of diseases caused by unrestrained immune reactions. Currently, pharmacological targeting of PI3Kgamma and/or PI3Kdelta represents one of the most promising challenges for companies interested in the development of novel safe treatments for inflammatory diseases. In this review we provide a general outline of PI3Kgamma- and PI3Kdelta-specific functions in distinct subsets of inflammatory cells. We also discuss the therapeutic impact of novel compounds targeting PI3Kgamma, PI3Kdelta or both, in mouse models of autoimmune disorders (systemic lupus erythematosus (SLE) and rheumatoid arthritis), respiratory diseases (allergic asthma and chronic obstructive pulmonary disease) and cardiovascular dysfunctions (atherosclerosis and myocardial infarction).
Ghigo
Alessandra
A
Molecular Biotechnology Center, University of Torino, Via Nizza 52, 10126 Torino, Italy.
Damilano
Federico
F
Molecular Biotechnology Center, University of Torino, Via Nizza 52, 10126 Torino, Italy.
Braccini
Laura
L
Molecular Biotechnology Center, University of Torino, Via Nizza 52, 10126 Torino, Italy.
Hirsch
Emilio
E
Molecular Biotechnology Center, University of Torino, Via Nizza 52, 10126 Torino, Italy.
D000818:Animals; D001249:Asthma / Q000188:drug therapy; D001327:Autoimmune Diseases / Q000188:drug therapy; D001402:B-Lymphocytes / Q000276:immunology; D002318:Cardiovascular Diseases / Q000188:drug therapy; D002634:Chemotaxis, Leukocyte / Q000502:physiology; D004804:Eosinophils / Q000276:immunology; D006801:Humans; D007107:Immune System / Q000201:enzymology; D007249:Inflammation / Q000188:drug therapy / Q000201:enzymology; D007962:Leukocytes / Q000276:immunology; D008407:Mast Cells / Q000276:immunology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D021122:Protein Subunits / Q000037:antagonists & inhibitors* / Q000378:metabolism; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy; D015398:Signal Transduction / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology
D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D021122:Protein Subunits