IL-7 inhibits dexamethasone-induced apoptosis via Akt/PKB in mature, peripheral T cells
✍ Scribed by Hadassah Sade; Apurva Sarin
- Publisher
- John Wiley and Sons
- Year
- 2003
- Tongue
- English
- Weight
- 185 KB
- Volume
- 33
- Category
- Article
- ISSN
- 0014-2980
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✦ Synopsis
Abstract
We have investigated the mechanism of IL‐7‐mediated inhibition of dexamethasone‐induced apoptosis in T cells. Broad‐spectrum caspase inhibitors block dexamethasone‐triggered nuclear fragmentation, but not the loss of mitochondrial transmembrane potential or membrane integrity in CD3^+^ mature T cells isolated from adult mouse spleens. IL‐7 blocked dexamethasone‐induced apoptosis and the processing of caspase‐3 and caspase‐7. IL‐7 also blocked dexamethasone‐triggered dephosphorylation of the serine‐threonine kinase Akt/PKB and its target, the Ser^136^ residue in Bad. The loss of anti‐apoptotic proteins Bcl‐x~L~ and inhibitor of apoptosis protein‐2 (IAP‐2) was also blocked by IL‐7. The protective effect was attenuated by pharmacological inhibitors of phosphatidylinositol‐3 kinase (PI3K) with one exception: inhibition of PI3K did not abrogate Bcl‐x~L~ expression in the presence of IL‐7. The anti‐apoptotic role of Akt suggested by these experiments was tested by overexpression of constitutively active Akt, which blocked dexamethasone‐induced apoptosis and elevated IAP‐2 but not Bcl‐x~L~ levels in a mature T cell line. Thus, IL‐7 regulates IAP‐2 expression and inhibits dexamethasone‐induced apoptosis by activating Akt via PI3K‐dependent signaling, but regulates Bcl‐x~L~ expression via a PI3K‐independent pathway in mature T cells.