Relationship between high-mobility group box 1 protein release and T-cell suppression in rats after thermal injury.
To study whether high-mobility group box 1 protein (HMGB1) has an effect on T-cell-mediated immunity secondary to burn injury, 96 male Wistar rats weighing 250 to 300 g were randomly divided into three groups as follows:sham burn group, burn group, and burn with ethyl pyruvate treatment group, and they were killed on postburn days (PBDs)1, 3, 5, and 7, respectively, with 8 animals at each time point. Columns of nylon wool were used to isolate splenic T cells. T-Cell proliferation was analyzed with thiazolyl blue and expression of IL-2 receptor alpha (IL-2Ralpha) on the surface of T cell with flow cytometry. Levels of HMGB1 were determined using Western blot analysis. IL-2, soluble IL-2R, IL-4, and interferon-gamma were determined with enzyme-linked immunosorbent assay kits. Gene expressions of HMGB1, IL-2, and IL-2R were assessed using reverse-transcription polymerase chain reaction, and activation of nuclear factor of activated T cell was determined with gel mobility shift assay. The levels of HMGB1 in plasma were significantly elevated on PBDs 1 to 5. Significant proliferation of splenic T cells and IL-2, as well as IL-2Ralpha expression on T cells, were simultaneously suppressed to a certain extent on PBDs 1 to 7. Nuclear factor of activated T-cell activity of splenic T cells was markedly down-regulated on PBDs 1 to 3. Administration of ethyl pyruvate to inhibit HMGB1 can significantly restore proliferative activity, nuclear factor of activated T-cell activity, and expression levels of IL-2 and IL-2Ralpha on T cells. High-mobility group box 1 protein released after major burns might be associated with the pathogenesis of immunosuppression in splenic T lymphocytes in rats.
Zhang
Li-tian
LT
Department of Microbiology and Immunology, Burns Institute, First Hospital Affiliated to the Chinese PLA General Hospital, Beijing, People's Republic of China.
Yao
Yong-ming
YM
Dong
Yue-Qing
YQ
Dong
Ning
N
Yu
Yan
Y
Sheng
Zhi-yong
ZY
D000818:Animals; D002056:Burns / Q000097:blood / Q000378:metabolism*; D017252:CD3 Complex / Q000096:biosynthesis; D049109:Cell Proliferation; D024243:HMGB1 Protein / Q000378:metabolism*; D006358:Hot Temperature; D007376:Interleukin-2 / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D013154:Spleen / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D013997:Time Factors
D017252:CD3 Complex; D024243:HMGB1 Protein; D007376:Interleukin-2; D015375:Receptors, Interleukin-2