[The role of Janus kinase-signal transducer and transcription activator pathway in the regulation of synthesis and release of lipopolysaccharide-induced high mobility group box-1 protein].
OBJECTIVE
To investigate the role of Janus kinase-signal transducer and transcription activator (JAK-STAT) pathway in the regulation of synthesis and release of lipopolysaccharide-induced high mobility group box-1 protein (HMGB1).


METHODS
Peritoneal macrophages harvested from male Wistar rats were incubated for 3 days before the experiment. The activation of Janus kinase-2 (JAK2), signal transducer and activator of transcription-1 (STAT1) and STAT3 was observed before and 10, 30, 60 and 120 mins after LPS stimulation (4 determinations at each time point) and it was expressed as A value (absorption). In addition, the cells were divided into normal control, LPS stimulation, JAK2 inhibition (with AG490 treatment 2 hours before LPS stimulation), STAT1 inhibition (with fludarabine treatment 2 hours before LPS stimulation) and STAT3 inhibition (with rapamycin treatment 2 hours before LPS stimulation) groups. The cells in all groups except control group were stimulated with LPS 3 days after culture. The expression of HMGB1 gene and its protein release in each group were determined for 4 times and were expressed as A value.


RESULTS
LPS could activate JAK2, STAT1 and STAT3 within 2 hours, especially the activation of STAT3 appeared more quickly, peaking at 10 minutes after LPS stimulation (7.47 +/- 0.56). Pretreatment with the inhibitors of JAK-STAT pathway could markedly reduce the expression of HMGB1 mRNA (P < 0.01), but exerted no effect on HMGB1 release.


CONCLUSIONS
JAK-STAT pathway can be activated early during endotoxin challenge, and it may play a role in the regulation of HMGB1 synthesis.
Fundermental Department of Burn Institute, 304th Hospital Affiliated to PLA General Hospital, Beijing 100037, P. R. China.
Hui
H
Liu
Yong-ming
YM
Yao
Yue-qing
YQ
Dong
Yan
Y
Yu
Zhi-yong
ZY
Sheng
D000818:Animals; D018929:Cell Culture Techniques; D024243:HMGB1 Protein / Q000096:biosynthesis*; D053614:Janus Kinase 2 / Q000378:metabolism*; D008070:Lipopolysaccharides; D017737:Macrophages, Peritoneal / Q000378:metabolism*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D050794:STAT1 Transcription Factor / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000378:metabolism*
D024243:HMGB1 Protein; C104200:Hbp1 protein, rat; D008070:Lipopolysaccharides; D050794:STAT1 Transcription Factor; D050796:STAT3 Transcription Factor; C494081:Stat1 protein, rat; C494088:Stat3 protein, rat; C507927:Jak2 protein, rat; D053614:Janus Kinase 2