Journal
SHOCK
Volume 30, Issue 4, Pages 449-455Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/SHK.0b013e3181672495
Keywords
high-mobility group box 1 protein; burns; IL-2; IL-2 receptors; splenic T cell
Funding
- National Basic Research Program of China [2005CB522602]
- National Natural Science Foundation [30672178]
- National Natural Science Outstanding Youth Foundation of China [30125020]
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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-2R alpha) 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-2R alpha 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-2R alpha 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.
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