Abstract
Glucocorticoids (GC) are widely used as antiinflammatory/immunosuppressive drugs and antitumor agents in several types of lymphoma and leukemia. Therapeutic doses of GC induce growth-suppressive and cytotoxic effects on various leukocytes including B cells. Molecularmechanisms of GCaction include induction of GC target genes. Glucocorticoidinduced leucine zipper (GILZ) is a rapidly, potently, and invariably GC-induced gene. It mediates a number of GC effects, such as control of cell proliferation, differentiation, and apoptosis. Here we show that deletion of GILZ in mice leads to an accumulation of B lymphocytes in the bone marrow, blood, and lymphoid tissues. Gilz knockout (KO) mice develop a progressive nonlethalBlymphocytosis,with expansion ofB2201 cells in the bone marrowand in the periphery, dependent on increased B-cell survival. Decreased B-cell apoptosis in mice lacking GILZ correlates with increased NF-kB transcriptional activity and Bcl-2 expression. B cell-specific gilz KO mice confirmed that the effect of GILZ deletion is B-cell self-intrinsic. These results establish GILZ as an important regulator of B-cell survival and suggest that the deregulation of GILZ expression could be implicated in the pathogenesis of B-cell disorders.
| Original language | English |
|---|---|
| Pages (from-to) | 1790-1801 |
| Number of pages | 12 |
| Journal | Blood |
| Volume | 126 |
| Issue number | 15 |
| DOIs | |
| Publication status | Published - Oct 8 2015 |
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ASJC Scopus subject areas
- Hematology
- Biochemistry
- Cell Biology
- Immunology
- Medicine(all)
Cite this
Lack of glucocorticoid-induced leucine zipper (GILZ) deregulates B-cell survival and results in B-cell lymphocytosis in mice. / Bruscoli, Stefano; Biagioli, Michele; Sorcini, Daniele; Frammartino, Tiziana; Cimino, Monica; Sportoletti, Paolo; Mazzon, Emanuela; Bereshchenko, Oxana; Riccardi, Carlo.
In: Blood, Vol. 126, No. 15, 08.10.2015, p. 1790-1801.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Lack of glucocorticoid-induced leucine zipper (GILZ) deregulates B-cell survival and results in B-cell lymphocytosis in mice
AU - Bruscoli, Stefano
AU - Biagioli, Michele
AU - Sorcini, Daniele
AU - Frammartino, Tiziana
AU - Cimino, Monica
AU - Sportoletti, Paolo
AU - Mazzon, Emanuela
AU - Bereshchenko, Oxana
AU - Riccardi, Carlo
PY - 2015/10/8
Y1 - 2015/10/8
N2 - Glucocorticoids (GC) are widely used as antiinflammatory/immunosuppressive drugs and antitumor agents in several types of lymphoma and leukemia. Therapeutic doses of GC induce growth-suppressive and cytotoxic effects on various leukocytes including B cells. Molecularmechanisms of GCaction include induction of GC target genes. Glucocorticoidinduced leucine zipper (GILZ) is a rapidly, potently, and invariably GC-induced gene. It mediates a number of GC effects, such as control of cell proliferation, differentiation, and apoptosis. Here we show that deletion of GILZ in mice leads to an accumulation of B lymphocytes in the bone marrow, blood, and lymphoid tissues. Gilz knockout (KO) mice develop a progressive nonlethalBlymphocytosis,with expansion ofB2201 cells in the bone marrowand in the periphery, dependent on increased B-cell survival. Decreased B-cell apoptosis in mice lacking GILZ correlates with increased NF-kB transcriptional activity and Bcl-2 expression. B cell-specific gilz KO mice confirmed that the effect of GILZ deletion is B-cell self-intrinsic. These results establish GILZ as an important regulator of B-cell survival and suggest that the deregulation of GILZ expression could be implicated in the pathogenesis of B-cell disorders.
AB - Glucocorticoids (GC) are widely used as antiinflammatory/immunosuppressive drugs and antitumor agents in several types of lymphoma and leukemia. Therapeutic doses of GC induce growth-suppressive and cytotoxic effects on various leukocytes including B cells. Molecularmechanisms of GCaction include induction of GC target genes. Glucocorticoidinduced leucine zipper (GILZ) is a rapidly, potently, and invariably GC-induced gene. It mediates a number of GC effects, such as control of cell proliferation, differentiation, and apoptosis. Here we show that deletion of GILZ in mice leads to an accumulation of B lymphocytes in the bone marrow, blood, and lymphoid tissues. Gilz knockout (KO) mice develop a progressive nonlethalBlymphocytosis,with expansion ofB2201 cells in the bone marrowand in the periphery, dependent on increased B-cell survival. Decreased B-cell apoptosis in mice lacking GILZ correlates with increased NF-kB transcriptional activity and Bcl-2 expression. B cell-specific gilz KO mice confirmed that the effect of GILZ deletion is B-cell self-intrinsic. These results establish GILZ as an important regulator of B-cell survival and suggest that the deregulation of GILZ expression could be implicated in the pathogenesis of B-cell disorders.
UR - http://www.scopus.com/inward/record.url?scp=84943649048&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84943649048&partnerID=8YFLogxK
U2 - 10.1182/blood-2015-03-631580
DO - 10.1182/blood-2015-03-631580
M3 - Article
C2 - 26276664
AN - SCOPUS:84943649048
VL - 126
SP - 1790
EP - 1801
JO - Blood
JF - Blood
SN - 0006-4971
IS - 15
ER -