Characterization of glucocorticoid receptor translocation, cytoplasmic IkappaB, nuclear NFkappaB, and activation of NFkappaB in T lymphocytes exposed to stress-inducible concentrations of corticosterone in vivo.
The present study was conducted to determine if selected events in glucocorticoid receptor (GR) signaling that have been identified using mostly in vitro approaches with synthetic glucocorticoids also occur in mature T cells exposed to relevant levels of corticosterone in vivo. In contrast to effects reported in vitro, corticosterone did not cause significant translocation of GR to the nucleus in splenic T cells, though it did increase the amount of nuclear GR in these cells capable of binding to a glucocorticoid response element. At most time points and dosages, corticosterone caused little or no change in cytoplasmic IkappaB or nuclear NFkappaB levels. Activation of T cells by anti-CD3 increased the amount of NFkappaB in the nucleus and decreased the amount of IkappaB in the cytoplasm. Corticosterone did not significantly inhibit the decrease in cytoplasmic IkappaB, but it did slightly diminish the increase in nuclear NFkappaB. The same dosages of corticosterone substantially suppressed anti-CD3-induced cytokine gene expression, indicating that a meaningful amount of glucocorticoid-mediated signaling (of some type) occurred in this experimental system. Thus, GR translocation per se seems not to be critical for GR-mediated signaling in vivo. Other considerations, such as the make-up of GR-containing complexes in the nucleus or unexpected sensitivity to small changes in total nuclear GR, may be important. Additionally, upregulation of IkappaB and consequent inhibition of NFkappaB activation are not prominent in vivo, in contrast to results obtained in vitro or with a synthetic glucocorticoid.[1]References
- Characterization of glucocorticoid receptor translocation, cytoplasmic IkappaB, nuclear NFkappaB, and activation of NFkappaB in T lymphocytes exposed to stress-inducible concentrations of corticosterone in vivo. Pruett, S.B., Fan, R., Zheng, Q. Int. Immunopharmacol. (2003) [Pubmed]
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