Arthritis :: GILZ mediates the antiinflammatory effects of glucocorticoids
Glucocorticoids are widely used as drugs to treat inflammatory conditions such as arthritis or dermatitis and they act in part by suppressing T cell function.
In a study appearing online on May 10 in advance of publication in the June print issue of the Journal of Clinical Investigation, Carlo Riccardo and colleagues from the University of Perugia show how the protein glucocorticoid-induced leucine zipper (GILZ) mediates the effects of the glucocorticoid dexamethasone.
Using a variety of biochemical and cellular approaches, the authors show that GILZ interacts directly with the signaling molecule Ras and forms a trimeric complex with Ras and another signaling protein Raf. Ras normally activates a number of signaling pathways involved in cell growth and survival, however the authors found that GILZ diminished the activation of Ras/Raf and in turn inhibited Ras- and Raf-dependent T cell proliferation. When GILZ was inactivated the antiproliferative effects of dexamethasone were inhibited, resulting in increased T cell proliferation.
Together, the data indicate that GILZ acts as a negative regulator of Ras- and Raf-induced cell proliferation and as an important mediator of the antiinflammatory effects of glucocorticoids.