Roles of brain cytokines in the adaptive responses to environmental stresses

脑细胞因子在环境应激适应性反应中的作用

• 批准号: 08457021
• 负责人: KATAFUCHI Toshihiko
• 金额: $ 4.8万
• 依托单位: KYUSHU UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1996
• 资助国家: 日本
• 起止时间: 1996 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08457021/
• 关键词: Fos protein; natural killer cell activity; splenic sympathetic nerve activity; immobilization stress; allergic contact dermatitis; long-term potentiation; NMDA receptor; Stem cell factor; 温度ストレス; リアルタイムPCR; 遅延型過敏症; グルココルチコイド; C-線維; 幹細胞増殖因子

We have investigated the roles of brain cyotokines in the stress responses to various environmental stimuli, and found that ;(1) Cytokines including IL-1beta and IFNalpha were expressed in the brain in response to not only inflammatory stresses but also non-inflammatory stresses such as immobilization (1MB) and heat or cold exposure.(2) Fos protein induced in rat medial preoptic area (MPO) in response to heat or cold exposure for 2 hours works to elevate body temperature since blockade of Fos expression by antisenseoligo DNA for c-fos mRNA results in the decrease in body temperature both in heat (33ﾟC) and cold (4ﾟC) exposure.(3) Splenic sympathetic nerve activity (SSNA) was suppressed by chemical stimulation of the lateral hypothalamic area (LHA) and enhanced by that of the ventromedial hypothalamic nucleus (VMH). In addition, since the prostaglandin E2 (PGE2)-induced activation of SSNA was blocked by a CRF antagonist, a-helical CRF, while the CRF-induce elevation of SSNA was not bloc … More ked by a cyclooxygenase inhibitor, salicylate, it is suggested that there is a sequential relationship between actions of CRF and PGE2, with an activation of PGE2 system followed by that of CRF in the brain.(4) Since the IMB-induced suppression of splenic NK cell activity in mice was attenuated by pretreatment with anti-IL-1beta neutralizing antibody, brain IL-1beta plays a significant role in the IMB-induced immunosuppression.(5)Adrenal glucocorticoids suppress the development of allergic contact dermatits (ACD), a prototype of T cell-dependent delayed type hypersensitivity, while they delay the termination of ACD in the presence of C-fibers.(6)Tumor necrosis factor-alpha (TNF-alpha) and IL-1beta suppress the neuronal activity in the VMH, and dorsal mortor nucleus of the vagus, respectively, probably affecting body temperature and gastric acid secretion.(7)Bath application of IL-6 resulted in a suppression of long-term potentiation in rat Schaffer collateral-CA pathway.(8)Glutamate induced an activation of NMDA receptor-mediated Ca^<2+>-dependent K^+ current in rat MPG neurons.(9)Stem cell factor modulated a paired-pulse facilitation like tetanic stimulation in mouse mossy fiber-CA3 pathway. Less

我们研究了大脑细胞因子在各种环境刺激下的应激反应中的作用，发现；(1)包括il -1 β和ifn α在内的细胞因子在大脑中表达，不仅响应炎症应激，也响应非炎症应激，如固定（1MB）和热或冷暴露。(2)热或冷暴露2小时后，大鼠内侧视前区（MPO）诱导的Fos蛋白可升高体温，因为C - Fos mRNA通过反感寡核苷酸阻断Fos的表达，导致热（33 C）和冷（4 C）暴露时体温均下降。(3)下丘脑外侧区（LHA）的化学刺激抑制了脾交感神经活动，下丘脑腹内侧核（VMH）的化学刺激增强了脾交感神经活动。此外，由于前列腺素E2 （PGE2）诱导的SSNA激活被一种CRF拮抗剂a-螺旋CRF阻断，而CRF诱导的SSNA升高并没有被一种环加氧酶抑制剂水杨酸酯阻断，这表明CRF和PGE2的作用之间存在顺序关系，大脑中PGE2系统的激活紧随CRF的激活。(4)由于imb对小鼠脾NK细胞活性的抑制可以通过抗il -1 β中和抗体预处理而减弱，因此，脑il -1 β在imb诱导的免疫抑制中起着重要作用。(5)肾上腺糖皮质激素抑制变应性接触性皮炎（ACD）的发展，ACD是T细胞依赖性延迟型超敏反应的原型，而它们在c -纤维存在时延迟ACD的终止。(6)肿瘤坏死因子- α (tnf - α)和il -1 β分别抑制迷走神经VMH和背运动核的神经元活性，可能影响体温和胃酸分泌。(7) IL-6对大鼠Schaffer侧枝- ca通路的长期增强作用有抑制作用。(8)谷氨酸诱导大鼠MPG神经元中NMDA受体介导的Ca^<2+>依赖性K^+电流的激活。(9)干细胞因子可调节小鼠苔藓纤维- ca3通路中类似破伤风刺激的成对脉冲促进。少

项目成果

片渕俊彦: "交感神経による脾臓ナチュラルキラー細胞活性制御機能の視床下部機序" 自律神経. 33(3). 267-272 (1996)

Toshihiko Katabuchi：“交感神经介导的脾脏自然杀伤细胞活性控制的下丘脑机制”自主神经学 33(3) 267-272 (1996)。

Katafuchi, T., Kondo, T., Take, S.and Hori, T.: "Hypothalamic modulation of delayed-type hypersensitivity and splenic natural killer cellactivity." Brain and the Bio-defense System. Edited by Y.Oomura and T.Hori, Japan Scientific Societies Press/S.Karger,

Katafuchi, T.、Kondo, T.、Take, S. 和 Hori, T.：“迟发型超敏反应和脾自然杀伤细胞活性的下丘脑调节”。

Katafuchi,T.: "Brain and the Bio-defense System." Japan Scientific Societies Press/S.Karger, 248 (1998)

Katafuchi,T.：“大脑和生物防御系统”。

片渕俊彦: "インターフェロン-その研究の歩みと臨床応用への可能性" ライフサイエンス, 211 (1998)

Toshihiko Katabuchi：“干扰素 - 其研究历史和临床应用潜力”生命科学，211 (1998)

Katafuchi,T.: "Differential effects of tumor necrosis factor-α and -β on the rat ventromedial hypothalami neurons in vitro." Am.J.Physiol.272. R1966-R1971 (1997)

Katafuchi, T.：“肿瘤坏死因子-α 和 -β 对大鼠腹内侧下丘脑神经元的体外影响。Am.J.Physiol.272 (1997)。