Inhibition of leptin-induced IL-1beta expression by glucocorticoids in the brain.
Leptin is an important circulating signal for the regulation of food intake and body weight. Glucocorticoids were suggested to play a physiological role in the feedback inhibition of immune/inflammatory responses. In the present study, we examined whether these neuroendocrine effects of glucocorticoids are linked to changes in the leptin-induced expression of IL-1beta and STAT3 activation in the brain. Intravenous injection of leptin induced IL-1beta expression in the hypothalamus. Pretreatment with dexamethasone dose dependently inhibited leptin-induced IL-1beta expression in the hypothalamus. Moreover, dexamethasone inhibited leptin-induced IL-1beta expression in the primary cultured glial cells. In contrast, pretreatment with dexamethasone did not inhibit leptin-induced STAT3 phosphorylation in the hypothalamus. These effects of dexamethasone may not be due to the change in the expression level of the leptin receptor Ob-Ra and Ob-Rb isoforms. Therefore, it is suggested that glucocorticoid negatively regulates leptin-induced IL-1beta expression in the brain.
Hosoi
Toru
T
Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Hokkaido University, Kita 12, Nishi 6, Kita-ku, 060-0812, Sapporo, Japan.
Okuma
Yasunobu
Y
Wada
Sachiyo
S
Nomura
Yasuyuki
Y
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000187:drug effects / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology*; D005247:Feeding Behavior / Q000502:physiology*; D005786:Gene Expression Regulation; D007031:Hypothalamus / Q000187:drug effects* / Q000502:physiology; D007375:Interleukin-1 / Q000096:biosynthesis*; D020738:Leptin / Q000494:pharmacology; D051379:Mice; D009457:Neuroglia / Q000187:drug effects; D010766:Phosphorylation / Q000187:drug effects; D011956:Receptors, Cell Surface / Q000096:biosynthesis / Q000187:drug effects; D054411:Receptors, Leptin; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050796:STAT3 Transcription Factor; D015534:Trans-Activators / Q000187:drug effects / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D004268:DNA-Binding Proteins; D007375:Interleukin-1; D020738:Leptin; D011956:Receptors, Cell Surface; D054411:Receptors, Leptin; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D015534:Trans-Activators; C515447:leptin receptor, mouse; D003907:Dexamethasone