Bacterial endotoxin induces STAT3 activation in the mouse brain.
In the present study, we investigated regulatory mechanisms of bacterial endotoxin-induced STAT3 activation in the brain. Intraperitoneal injection of lipopolysaccharide (LPS) dose-dependently (0.5-5000 microg/kg) induced STAT3 phosphorylation in the hypothalamus. LPS-induced STAT3 phosphorylation was peaked at 2-4 h and declined there after. Moreover, intracerebroventricular injection of LPS induced STAT3 phosphorylation in the cortex and the hippocampus, indicating that central as well as peripheral LPS can act in the brain to induce STAT3 activation. Glucocorticoids are known to play a physiological role in the feedback inhibition of immune/inflammatory responses in the endocrine system. Interestingly, we observed no effect of dexamethasone on LPS-induced STAT3 phosphorylation in the hypothalamus. These findings point to the important role of STAT3 in the neuroimmune interaction of inflammation in the brain.
Hosoi
Toru
T
Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Hokkaido University, Kita 12, Nishi 6, Kita-Ku, Sapporo 060-0812, Japan.
Okuma
Yasunobu
Y
Kawagishi
Toru
T
Qi
Xin
X
Matsuda
Tadashi
T
Nomura
Yasuyuki
Y
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D008070:Lipopolysaccharides / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D010766:Phosphorylation; D050796:STAT3 Transcription Factor; D015398:Signal Transduction / Q000187:drug effects; D015534:Trans-Activators / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*
D004268:DNA-Binding Proteins; D008070:Lipopolysaccharides; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D015534:Trans-Activators