Cyclooxygenase-2 blockade inhibits accumulation and function of myeloid-derived suppressor cells and restores T cell response after traumatic stress.
10.1007/s11596-014-1264-6
- Author:
Ren-jie LI
1
;
Lin LIU
;
Wei GAO
;
Xian-zhou SONG
;
Xiang-jun BAI
;
Zhan-fei LI
Author Information
1. Department of Traumatic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China, lirenjiejiayou@126.com.
- Publication Type:Journal Article
- MeSH:
Animals;
Apoptosis;
drug effects;
Arginase;
biosynthesis;
CD11b Antigen;
biosynthesis;
CD4-Positive T-Lymphocytes;
drug effects;
metabolism;
Cell Proliferation;
drug effects;
Cyclooxygenase 2;
biosynthesis;
Cyclooxygenase 2 Inhibitors;
administration & dosage;
Gene Expression Regulation;
drug effects;
Humans;
Mice;
Myeloid Progenitor Cells;
metabolism;
pathology;
Nitrobenzenes;
administration & dosage;
Stress Disorders, Traumatic;
drug therapy;
genetics;
pathology;
Sulfonamides;
administration & dosage
- From:
Journal of Huazhong University of Science and Technology (Medical Sciences)
2014;34(2):234-240
- CountryChina
- Language:English
-
Abstract:
Myeloid-derived suppressor cells (MDSCs) play a crucial role in T cell dysfunction, which is related to poor outcome in patients with severe trauma. Cyclooxygenase-2 (Cox-2) contributes to immune disorder in trauma and infection via production of prostaglandin E2. However, the role of Cox-2 in the accumulation and function of MDSCs after traumatic stress has not been fully elucidated. In the present study, we treated murine trauma model with NS398, a selective Cox-2 inhibitor. Then the percentages of CD11b+/Gr-1+ cells, proliferation and apoptosis of CD4+ T cells were determined. Arginase activity and arginase-1 (Arg-1) protein expression of splenic CD11b+/Gr-1+ cells, and delayed-type hypersensitivity (DTH) response were analyzed. The results showed that Cox-2 blockade significantly decreased the percentages of CD11b+/Gr-1+ cells in the spleen and bone marrow 48 and 72 h after traumatic stress. NS398 inhibited arginase activity and down-regulated the Arg-1 expression of splenic CD11b+/Gr-1+ cells. Moreover, NS398 could promote proliferation and inhibit apoptosis of CD4+ T cells. It also restored DTH response of traumatic mice. Taken together, our data revealed that Cox-2 might play a pivotal role in the accumulation and function of MDSC after traumatic stress.
