Acute stress induces the rapid and transient induction of caspase-1, gasdermin D and release of constitutive IL-1β protein in dorsal hippocampus.
Acute stress induces the rapid and transient induction of caspase-1, gasdermin D and release of constitutive IL-1β protein in dorsal hippocampus.
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DOI：
10.1016/j.bbi.2020.07.042
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发表时间：
2020-11
期刊：
影响因子：
--
通讯作者：
Maier SF
中科院分区：
文献类型：
--
作者：
Frank MG;Baratta MV;Zhang K;Fallon IP;Pearson MA;Liu G;Hutchinson MR;Watkins LR;Goldys EM;Maier SF
促炎细胞因子白细胞介素（IL）-1β在行为表现中起关键作用（即，疾病）的应激反应。事实上，暴露于急性和慢性应激源诱导应激敏感脑区中IL-1β的表达。因此，通常推测暴露于应激物诱导脑实质中IL-1β的细胞外释放。然而，这种应激诱发的神经免疫现象尚未被直接证实，也没有在脑中表征IL-1β释放到细胞外环境中的细胞过程。该细胞过程涉及一种称为焦亡的炎性细胞死亡形式，其涉及：1）半胱天冬酶-1的活化，2）IL-1β的半胱天冬酶-1成熟，3）gasdermin D（GSDMD）的半胱天冬酶-1裂解，和4）GSDMD诱导的细胞膜的渗透性，IL-1β通过该渗透性释放到细胞外空间中。因此，本研究检测了应激是否诱导IL-1β的细胞外释放，以及是否参与上述细胞过程介导脑中IL-1β的释放。雄性Sprague-Dawley大鼠暴露于不可避免的尾电击（IS）。检测背侧海马IL-1β细胞外释放、caspase-1活性及GSDMD裂解。我们发现，暴露于IS诱导IL-1β释放到细胞外空间的短暂增加后立即终止的压力。在IL-1β释放之前，IS还诱导caspase-1活性的短暂增加，而在终止应激后立即观察到GSDMD的激活。IS还增加了ESCRTIII蛋白CHMP 4 B的mRNA和蛋白表达，该蛋白参与细胞修复。本研究结果表明，暴露于急性应激诱导脑内的焦亡的标志，这可能是一个关键的细胞过程，参与释放IL-1β到脑实质的细胞外环境。
The proinflammatory cytokine interleukin (IL)-1β plays a pivotal role in the behavioral manifestations (i.e., sickness) of the stress response. Indeed, exposure to acute and chronic stressors induces the expression of IL-1β in stress-sensitive brain regions. Thus, it is typically presumed that exposure to stressors induces the extra-cellular release of IL-1β in the brain parenchyma. However, this stress-evoked neuroimmune phenomenon has not been directly demonstrated nor has the cellular process of IL-1β release into the extracellular milieu been characterized in brain. This cellular process involves a form of inflammatory cell death, termed pyroptosis, which involves: 1) activation of caspase-1, 2) caspase-1 maturation of IL-1β, 3) caspase-1 cleavage of gasdermin D (GSDMD), and 4) GSDMD-induced permeability of the cell membrane through which IL-1β is released into the extracellular space. Thus, the present study examined whether stress induces the extra-cellular release of IL-1β and engages the above cellular process in mediating IL-1β release in the brain. Male Sprague-Dawley rats were exposed to inescapable tailshock (IS). IL-1β extra-cellular release, caspase-1 activity and cleavage of GSDMD were measured in dorsal hippocampus. We found that exposure to IS induced a transient increase in the release of IL-1β into the extracellular space immediately after termination of the stressor. IS also induced a transient increase in caspase-1 activity prior to IL-1β release, while activation of GSDMD was observed immediately after termination of the stressor. IS also increased mRNA and protein expression of the ESCRTIII protein CHMP4B, which is involved in cellular repair. The present results suggest that exposure to an acute stressor induces the hallmarks of pyroptosis in brain, which might serve as a key cellular process involved in the release of IL-1β into the extracellular milieu of the brain parenchyma.
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影响因子：
32.4
作者：
Evavold CL;Ruan J;Tan Y;Xia S;Wu H;Kagan JC
通讯作者：
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影响因子：
16.2
作者：
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通讯作者：
Dong, Hong-Wei
DOI：
10.1073/pnas.1607769113
发表时间：
2016-07-12
影响因子：
11.1
作者：
Aglietti, Robin A.;Estevez, Alberto;Dueber, Erin C.
通讯作者：
Dueber, Erin C.
影响因子：
5.1
作者：
Alcocer-Gomez, Elisabet;Ulecia-Moron, Cristina;Cordero, Mario D.
通讯作者：
Cordero, Mario D.
影响因子：
2.9
作者：
CHOMCZYNSKI, P;SACCHI, N
通讯作者：
SACCHI, N