The study of modulation of brain-immune function and searching for new functional molecule regulated by leptin receptor

已知瘦素是调节食物摄入和体重的重要循环信号。这些作用被认为是通过下丘脑中枢通过Ob-Rb受体介导的。我们发现，外周应用瘦素增加白细胞介素（IL）-1b转录在大脑的许多地区。虽然瘦素没有诱导STAT 3激活或细胞因子信号转导抑制因子3（SOCS 3）表达在db/db小鼠的下丘脑，缺乏一个功能性的Ob-Rb受体，瘦素增加IL-1b水平的程度与正常小鼠相似。因此，瘦素的一个新的功能被认为是通过STAT 3非依赖性机制诱导IL-1b在脑的许多区域的表达。虽然瘦素受体存在于脑的许多区域，但除了下丘脑之外，很少有关于瘦素靶位点的体内功能研究。我们证明，外周应用瘦素不仅增加了下丘脑中STAT 3的磷酸化，而且也增加了下丘脑中STAT 3的磷酸化。 关于我们 通过蛋白质印迹法评估脑干。免疫组化这些发现代表了生理功能的瘦素Ob-Rb受体在脑干以及在下丘脑。糖皮质激素被建议在免疫/炎症反应的反馈抑制中发挥生理作用地塞米松预处理剂量依赖性地抑制瘦素诱导的IL-1b在下丘脑的表达。此外，地塞米松抑制瘦素诱导的原代培养的胶质细胞中IL-1b的表达。与此相反，地塞米松预处理不抑制瘦素诱导的STAT 3磷酸化在下丘脑。因此，糖皮质激素负性调节瘦素诱导的IL-1b在脑中的表达。我们研究了双链RNA激活的蛋白激酶（PKR）作为瘦素可能的信号通路的作用。PKR抑制剂2-氨基嘌呤抑制瘦素诱导的细胞内信号传导。然而，我们观察到瘦素并不激活PK，并且发现2-氨基嘌呤抑制瘦素信号传导的作用位点是Janus激酶。少

Leptin is known to be an important circulating signal for regulation of food intake and body weight. These effects were suggested to be mediated through the hypothalamic center via the Ob-Rb receptor. We found that peripherally applied leptin increased Interleukin (IL)-1b transcripts in many regions of the brain. Although leptin did not induce STAT3 activation or suppressor of cytokine signaling3 (SOCS3) expression in the hypothalamus of the db/db mice, which lack a functional Ob-Rb receptor, leptin increased the IL-1b levels to similar extents as normal mice. Therefore, a novel function of leptin is suggested as the induction of IL-1b expression in many regions of the brain via STAT3-independent mechanisms.Although leptin receptors exist in many regions of the brain, there have been few in vivo functional studies of leptin's target site other than the hypothalamus. We demonstrated that peripherally applied leptin increased STAT3 phosphorylation not only in the hypothalamus but also in … More the brainstem as assessed by Western blotting and. Immunohistochemistry. These findings represent physiologically functional leptin Ob-Rb receptor in the brainstem as well as in the hypothalamus.Glucocorticoids were suggested to play a physiological role in the feedback inhibition of immune/inflammatory responses Pretreatment with dexamethasone dose dependently inhibited leptin-induced IL-1b expression in the hypothalamus. Moreover, dexamethasone inhibited leptin-induced IL-1b expression in the primary cultured glial cells. In contrast, pretreatment with dexamethasone did not inhibit leptin-induced STAT3 phosphorylation in the hypothalamus. Therefore, it is suggested that glucocorticoid negatively regulates leptin-induced IL-1b expression in the brain.We investigated role of double-stranded RNA-activated protein kinase (PKR) as a possible signaling pathway of leptin. 2-aminopurine, an inhibitor of PKR inhibited leptin-induced intracellular signaling. However, we observed that leptin did not activate PK, and found the site of action of 2-aminopurine to inhibit leptin signaling was Janus kinase. Less