Endogenous glucocorticoids promote the expansion of myeloid-derived             suppressor cells in a murine model of trauma.
Stress-dose of glucocorticoid has been demonstrated to be beneficial for trauma patients in clinical studies. Recently, a heterogeneous population of myeloid cells with immunosuppressive activity named myeloid-derived suppressor cells (MDSCs) has been found to accumulate in the trauma host and can be induced by glucocorticoids in vitro. In order to explore the effect of endogenous glucocorticoids on MDSCs under trauma conditions, we blocked the glucocorticoid signal in a murine trauma model using the antagonist of the glucocorticoid receptor RU486 (mifepristone). We found for the first time that RU486 not only blunted MDSC expansion induced by trauma in the spleen, peripheral blood and bone marrow especially at 6 h after traumatic stress but also decreased the survival rate from 100 to 20% in traumatic mice within 7 days. Moreover, neither MDSCs producing arginase-1 nor the morphological characterization of trauma-induced MDSCs was affected by the blockage of the glucocorticoid receptor. Our results suggest that endogenous glucocorticoids may promote MDSCs expansion in a murine trauma model and MDSCs may be beneficial for the trauma host.
Department of Trauma Surgery, Tongji Hospital, Tongji Medical                     College, Huazhong University of Science and Technology, Wuhan, P.R. China.
Kun
K
Zhang
Xiangjun
X
Bai
Renjie
R
Li
Zhengzheng
Z
Xiao
Jiajun
J
Chen
Fan
F
Yang
Zhanfei
Z
Li
D000818:Animals; D001119:Arginase / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D039481:CD11b Antigen / Q000378:metabolism; D002478:Cells, Cultured; D005938:Glucocorticoids / Q000037:antagonists & inhibitors / Q000378:metabolism*; D007962:Leukocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D015735:Mifepristone / Q000494:pharmacology; D022423:Myeloid Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000378:metabolism; D013154:Spleen / Q000187:drug effects / Q000378:metabolism; D014947:Wounds and Injuries / Q000378:metabolism* / Q000401:mortality
D039481:CD11b Antigen; D005938:Glucocorticoids; D011956:Receptors, Cell Surface; C551746:granulocyte receptor 1, mouse; D015735:Mifepristone; D001119:Arginase