| First Author | Zhang TY | Year | 2005 |
| Journal | J Immunol | Volume | 174 |
| Issue | 2 | Pages | 879-89 |
| PubMed ID | 15634910 | Mgi Jnum | J:95835 |
| Mgi Id | MGI:3527383 | Doi | 10.4049/jimmunol.174.2.879 |
| Citation | Zhang TY, et al. (2005) The expression of 11beta-hydroxysteroid dehydrogenase type I by lymphocytes provides a novel means for intracrine regulation of glucocorticoid activities. J Immunol 174(2):879-89 |
| abstractText | The 11beta-hydroxysteroid dehydrogenase (11beta-HSD) enzymes control the interconversion of active glucocorticoids (GCS) and their inactive 11-keto metabolites, a process commonly referred to as the cortisone/cortisol shuttle. Although the prereceptor metabolism of GCS by 11beta-HSD is well documented in a variety of cells and tissues, it has not yet been carefully investigated in the major cell types of the immune system. In this study, we demonstrate that 11beta-HSD1 transcripts, protein, and enzyme activities are actively expressed in murine CD4(+), CD8(+), and B220(+) lymphocytes, as well as CD11c(+) dendritic cells. Only reductase activity was observed in living cells, evidenced by the restricted conversion of cortisone to cortisol. Activation of CD4(+) T cells increased their 11beta-HSD1 activity, as did their polarization into Th1 or Th2 cells. CD4(+) T cells isolated from aged donors (>16 mo) had increased 11beta-HSD1 protein and an elevated capacity to convert cortisone to cortisol. The GCS generated in murine CD4(+) T cells from their inactive 11-keto metabolites could activate the GCS receptor, demonstrated by an up-regulation of IL-7Ralpha and GCS-induced leucine zipper gene expression. The presence of a functional 11beta-HSD1 provides lymphocytes with a novel intracrine regulatory mechanism that could influence such processes as lymphocyte development, effector function, and susceptibility to apoptosis. Thus, the presence of 11beta-HSD1 provides an additional means to facilitate GCS influences over lymphocyte activities, uncoupled from the plasma concentration of GCS. |
