TY - JOUR
T1 - Cutting edge
T2 - IRF8 regulates bax transcription in vivo in primary myeloid cells
AU - Yang, Jine
AU - Hu, Xiaolin
AU - Zimmerman, Mary
AU - Torres, Christina M.
AU - Yang, Dafeng
AU - Smith, Sylvia B.
AU - Liu, Kebin
PY - 2011/11/1
Y1 - 2011/11/1
N2 - A prominent phenotype of IRF8 knockout (KO) mice is the uncontrolled expansion of immature myeloid cells. The molecular mechanism underlying this myeloproliferative syndrome is still elusive. In this study, we observed that Bax expression level is low in bone marrow preginitor cells and increases dramatically in primary myeloid cells in wt mice. In contrast, Bax expression level remained at a low level in primarymyeloid cells in IRF8 KO mice. However, in vitro IRF8 KO bone marrow-differentiated myeloid cells expressed Bax at a level as high as that in wild type myeloid cells. Furthermore, we demonstrated that IRF8 specifically binds to the Bax promoter region in primary myeloid cells. Functional analysis indicated that IRF8 deficiency results in increased resistance of the primary myeloid cells to Fas-mediated apoptosis. Our findings show that IRF8 directly regulates Bax transcription in vivo, but not in vitro during myeloid cell lineage differentiation.
AB - A prominent phenotype of IRF8 knockout (KO) mice is the uncontrolled expansion of immature myeloid cells. The molecular mechanism underlying this myeloproliferative syndrome is still elusive. In this study, we observed that Bax expression level is low in bone marrow preginitor cells and increases dramatically in primary myeloid cells in wt mice. In contrast, Bax expression level remained at a low level in primarymyeloid cells in IRF8 KO mice. However, in vitro IRF8 KO bone marrow-differentiated myeloid cells expressed Bax at a level as high as that in wild type myeloid cells. Furthermore, we demonstrated that IRF8 specifically binds to the Bax promoter region in primary myeloid cells. Functional analysis indicated that IRF8 deficiency results in increased resistance of the primary myeloid cells to Fas-mediated apoptosis. Our findings show that IRF8 directly regulates Bax transcription in vivo, but not in vitro during myeloid cell lineage differentiation.
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U2 - 10.4049/jimmunol.1101034
DO - 10.4049/jimmunol.1101034
M3 - Article
C2 - 21949018
AN - SCOPUS:80555154915
SN - 0022-1767
VL - 187
SP - 4426
EP - 4430
JO - Journal of Immunology
JF - Journal of Immunology
IS - 9
ER -