Association between high-mobility group box-1 protein release and immune function of dendritic cells in thermal injury.
The present study was performed to investigate in vivo the effect of high-mobility group box-1 protein (HMGB1) on the maturation of dendritic cell (DC) and the influence on T-cell-mediated immunity after thermal injury. Rats were randomly divided into 3 groups as follows: sham burn group, burn group, and burn with ethyl pyruvate (EP) treatment group, and they were sacrificed on post burn days (PBD) 1, 3, 5, and 7 respectively. MACS microbeads were used to isolate splenic DCs and column of nylon wool to obtain T cells. Phenotypes were analyzed by flow cytometry and cytokines were determined with ELISA kits. The expression levels of splenic HMGB1 were significantly elevated during PBD 1-7. DC expressed similar CD80 levels, strongly enhanced CD86, and slightly elevated MHC class II levels in comparison to DC from sham-injured rats, and protein levels of IL-12 were not increased after thermal injury. Administration of EP to inhibit HMGB1 could significantly enhance expression levels of CD80, MHC class II on DC surface, and IL-12 production after burns. Simultaneously, proliferative activity and expression levels of IL-2 as well as IL-2R alpha of T cell were restored. These results suggested that the excessively released HMGB1 might stimulate splenic DC to mature abnormally and down-regulate the IL-12 production, and further shifting of Th1 to Th2 with suppression of T-lymphocyte immune function following burn injury.
Department of Microbiology and Immunology, Burns Institute, First Hospital Affiliated to the Chinese PLA General Hospital, Beijing, People's Republic of China.
Li-Tian
LT
Zhang
Yong-Ming
YM
Yao
Feng-Hua
FH
Yao
Li-Feng
LF
Huang
Ning
N
Dong
Yan
Y
Yu
Zhi-Yong
ZY
Sheng
D000818:Animals; D002056:Burns / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D024243:HMGB1 Protein / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D011773:Pyruvates / Q000008:administration & dosage; D051381:Rats; D017208:Rats, Wistar; D013154:Spleen / Q000473:pathology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D058408:Th1-Th2 Balance; D015854:Up-Regulation / Q000187:drug effects / Q000276:immunology
D016207:Cytokines; D024243:HMGB1 Protein; D011773:Pyruvates; C046522:ethyl pyruvate