IL-7 inhibits dexamethasone-induced apoptosis via Akt/PKB in mature, peripheral T cells

Sade, Hadassah ; Sarin, Apurva (2003) IL-7 inhibits dexamethasone-induced apoptosis via Akt/PKB in mature, peripheral T cells European Journal of Immunology, 33 (4). pp. 913-919. ISSN 0014-2980

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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 Ser136 residue in Bad. The loss of anti-apoptotic proteins Bcl-xL 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-xL 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-xL 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-xL expression via a PI3K-independent pathway in mature T cells.

Item Type:Article
Source:Copyright of this article belongs to John Wiley and Sons.
Keywords:Apoptosis; T cell; IL-7; Corticosteroid; PI3K
ID Code:62143
Deposited On:19 Sep 2011 11:49
Last Modified:19 Sep 2011 11:49

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