Interleukin-1 beta converting enzyme is necessary for development of depression-like behavior following intracerebroventricular administration of lipopolysaccharide to mice.
Interleukin-1 beta converting enzyme is necessary for development of depression-like behavior following intracerebroventricular administration of lipopolysaccharide to mice.
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DOI：
10.1186/1742-2094-10-54
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发表时间：
2013-05-01
影响因子：
9.3
通讯作者：
Kelley KW
中科院分区：
文献类型：
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作者：
Lawson MA;McCusker RH;Kelley KW
白细胞介素-1 β转化酶（ICE，caspase 1）是一种半胱氨酸蛋白酶，可将未成熟的pro-IL-1β转化为活性成熟的IL-1β。IL-1β是一种促炎细胞因子，介导对炎症的许多生理和行为反应。ICE的基因缺失先前已显示可防止对脂多糖（LPS）诱导的炎症的一些负面生理反应。在这里，我们使用了一个临床前小鼠模型，以测试的假设，ICE是必要的抑郁样行为的发展后，脑室内（ICV）治疗LPS。成年雄性ICE敲除（ICE KO）和同源野生型C57 BL/6 J（WT）小鼠以100 ng/小鼠ICV或以830 μg/kg体重腹膜内（IP）施用LPS或等体积的盐水作为对照。在治疗后48小时内监测小鼠的疾病和抑郁样行为。给予ICV的LPS诱导WT和ICE KO小鼠的体重减轻。这种疾病反应在WT和ICE KO小鼠之间相似。正如预期的那样，ICV给药的LPS增加了WT小鼠在强迫游泳试验（FST）中的不动性并降低了蔗糖偏好，但在ICE KO小鼠中没有观察到这两种抑郁样行为的任何一种变化。ICV给予LPS后24 h，ICE-KO小鼠脑中TNF-α和CD 11b的表达低于WT小鼠。相反，当全身给予LPS时，两种小鼠的疾病反应、抑郁样行为和这些基因的表达是相似的。这些发现表明ICE在由中枢炎症刺激诱导的抑郁样行为中起特定作用，即使当全身施用LPS时不需要ICE。
Interleukin-1 beta converting enzyme (ICE, caspase 1) is a cysteine protease that processes immature pro-IL-1β into active mature IL-1β. IL-1β is a pro-inflammatory cytokine that mediates many of the physiological and behavioral responses to inflammation. Genetic deletion of ICE has previously been shown to prevent some negative physiologic responses to lipopolysaccharide (LPS)-induced inflammation. Here we used a preclinical murine model to test the hypothesis that ICE is necessary for development of depression-like behaviors following intracerebroventricular (ICV) treatment with LPS. Adult male ICE knockout (ICE KO) and congenic wild-type C57BL/6 J (WT) mice were administered LPS either ICV at 100 ng/mouse or intraperitoneally (IP) at 830 μg/kg body weight or an equal volume of saline as controls. Mice were monitored up to 48 h after treatment for both sickness and depression-like behaviors. LPS given ICV induced a loss of body weight in both WT and ICE KO mice. This sickness response was similar between WT and ICE KO mice. As expected, LPS administered ICV increased immobility in the forced swim test (FST) and decreased sucrose preference in WT mice but no change in either of these two depression-like behaviors was observed in ICE KO mice. Expression of TNF-α and CD11b in brain was lower in ICE-KO mice at 24 h following ICV administration of LPS compared to WT mice. In contrast, when LPS was given systemically, sickness response, depression-like behaviors, and expression of these genes were similar between the two strains of mice. These findings indicate that ICE plays a specific role in depression-like behavior induced by a central inflammatory stimuli even though it is not required when LPS is administered systemically.
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DOI：
10.1152/ajpregu.1998.274.6.r1829
发表时间：
1998-06-01
影响因子：
2.8
作者：
Burgess, W;Gheusi, G;Kelley, KW
通讯作者：
Kelley, KW
影响因子：
4.7
作者：
Kaster, Manuella P.;Gadotti, Vinicius M.;Rodrigues, Ana Lucia S.
通讯作者：
Rodrigues, Ana Lucia S.
影响因子：
14
作者：
Brookmeyer, Ron;Johnson, Elizabeth;Arrighi, H. Michael
通讯作者：
Arrighi, H. Michael
影响因子：
11
作者：
Goshen, I.;Kreisel, T.;Yirmiya, R.
通讯作者：
Yirmiya, R.
影响因子：
30.5
作者：
通讯作者：
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