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IL-7 inhibits dexamethasone-induced apoptosis via Akt/PKB in mature, peripheral T cells.
Eur J Immunol. 2003 Apr; 33(4):913-9.EJ

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.

Authors+Show Affiliations

National Centre for Biological Sciences, UAS-GKVK Campus, Bangalore, India.No affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

12672057

Citation

Sade, Hadassah, and Apurva Sarin. "IL-7 Inhibits Dexamethasone-induced Apoptosis Via Akt/PKB in Mature, Peripheral T Cells." European Journal of Immunology, vol. 33, no. 4, 2003, pp. 913-9.
Sade H, Sarin A. IL-7 inhibits dexamethasone-induced apoptosis via Akt/PKB in mature, peripheral T cells. Eur J Immunol. 2003;33(4):913-9.
Sade, H., & Sarin, A. (2003). IL-7 inhibits dexamethasone-induced apoptosis via Akt/PKB in mature, peripheral T cells. European Journal of Immunology, 33(4), 913-9.
Sade H, Sarin A. IL-7 Inhibits Dexamethasone-induced Apoptosis Via Akt/PKB in Mature, Peripheral T Cells. Eur J Immunol. 2003;33(4):913-9. PubMed PMID: 12672057.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - IL-7 inhibits dexamethasone-induced apoptosis via Akt/PKB in mature, peripheral T cells. AU - Sade,Hadassah, AU - Sarin,Apurva, PY - 2003/4/3/pubmed PY - 2003/5/8/medline PY - 2003/4/3/entrez SP - 913 EP - 9 JF - European journal of immunology JO - Eur J Immunol VL - 33 IS - 4 N2 - 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. SN - 0014-2980 UR - https://www.unboundmedicine.com/medline/citation/12672057/IL_7_inhibits_dexamethasone_induced_apoptosis_via_Akt/PKB_in_mature_peripheral_T_cells_ L2 - https://doi.org/10.1002/eji.200323782 DB - PRIME DP - Unbound Medicine ER -