Effect of inhibitors of signal transducer and activator of transcription-1/3 on expression of tumor necrosis factor-alpha induced by high mobility group box-1 protein inflammatory response in rat peritoneal macrophages.
- Author:
Hui LIU
1
;
Yong-ming YAO
;
Yan YU
;
Zhi-yong SHENG
Author Information
- Publication Type:Journal Article
- MeSH: Animals; Cells, Cultured; Drug Interactions; HMGB1 Protein; pharmacology; Macrophages, Peritoneal; drug effects; metabolism; Male; Rats; Rats, Wistar; STAT1 Transcription Factor; antagonists & inhibitors; STAT3 Transcription Factor; antagonists & inhibitors; Signal Transduction; Sirolimus; pharmacology; Transcription, Genetic; Tumor Necrosis Factor-alpha; biosynthesis; genetics; Vidarabine; analogs & derivatives; pharmacology
- From: Chinese Journal of Surgery 2006;44(3):193-197
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo investigate the inflammatory signal transduction of high mobility group box-1 protein (HMGB1) induced inflammatory response in rat peritoneal macrophages.
METHODSPeritoneal macrophages obtained from male Wistar rats were seeded in 24-well (1 x 10(6) cells/well) tissue culture plates. The cells were incubated for 3 days before they were stimulated with HMGB1, and treated with Fludarabine [the specific inhibitor of signal transducer and activator of transcription 1 (STAT1)] or Rapamycin (the specific inhibitor of STAT3). The time-dependent and dose-dependent responses between HMGB1 stimulation and tumor necrosis factor-alpha (TNF-alpha) gene expression as well as release were analyzed respectively. Moreover, the effect of Fludarabine and Rapamycin on TNF-alpha mRNA expression and protein release were also observed.
RESULTS(1) After HMGB1 challenge, TNF-alpha mRNA expressions were up-regulated markedly, peaked at 24 hours, and decreased at 36 hours. When HMGB1 was used at a concentration of 10 microg/ml, TNF-alpha mRNA expression increased most markedly. (2) HMGB1 could induce TNF-alpha release in rat peritoneal macrophages, with peaking at 4 hours and decreasing at 8 hours later. When the concentration of HMGB1 stimulation increased from 5 microg/ml to 25 microg/ml, TNF-alpha release was persistently enhanced. (3) It was also showed that TNF-alpha mRNA expression was significantly inhibited by treatment of either Fludarabine (100 micromol/L) or Rapamycin (25 ng/ml), while TNF-alpha release was not markedly suppressed.
CONCLUSIONSSTAT1 and STAT3 might be involved in the regulation of TNF-alpha gene expression, but not in TNF-alpha early release (< 24 hours) induced by HMGB1 stimulation in rat peritoneal macrophages.
