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Pyroptotic and non-pyroptotic effector functions of caspase-11.
Immunological Reviews ( IF 7.5 ) Pub Date : 2020-08-01 , DOI: 10.1111/imr.12910
Arwa Abu Khweek 1 , Amal O Amer 2
Affiliation  

Innate immune cells, epithelial cells, and many other cell types are capable of detecting infection or tissue injury, thus mounting regulated immune response. Inflammasomes are highly sophisticated and effective orchestrators of innate immunity. These oligomerized multiprotein complexes are at the center of various innate immune pathways, including modulation of the cytoskeleton, production and maturation of cytokines, and control of bacterial growth and cell death. Inflammasome assembly often results in caspase‐1 activation, which is an inflammatory caspase that is involved in pyroptotic cell death and release of inflammatory cytokines in response to pathogen patterns and endogenous danger stimuli. However, the nature of stimuli and inflammasome components are diverse. Caspase‐1 activation mediated release of mature IL‐1β and IL‐18 in response to canonical stimuli initiated by NOD‐like receptor (NLR), and apoptosis‐associated speck‐like protein containing a caspase recruitment domain (ASC). On the other hand, caspase‐11 delineates a non‐canonical inflammasome that promotes pyroptotic cell death and non‐pyroptotic functions in response to non‐canonical stimuli. Caspase‐11 in mice and its homologues in humans (caspase‐4/5) belong to caspase‐1 family of cysteine proteases, and play a role in inflammation. Knockout mice provided new genetic tools to study inflammatory caspases and revealed the role of caspase‐11 in mediating septic shock in response to lethal doses of lipopolysaccharide (LPS). Recognition of LPS mediates caspase‐11 activation, which promotes a myriad of downstream effects that include pyroptotic and non‐pyroptotic effector functions. Therefore, the physiological functions of caspase‐11 are much broader than its previously established roles in apoptosis and cytokine maturation. Inflammation induced by exogenous or endogenous agents can be detrimental and, if excessive, can result in organ and tissue damage. Consequently, the existence of sophisticated mechanisms that tightly regulate the specificity and sensitivity of inflammasome pathways provides a fine‐tuning balance between adequate immune response and minimal tissue damage. In this review, we summarize effector functions of caspase‐11.

中文翻译:

caspase-11 的焦亡和非焦亡效应子功能。

先天免疫细胞、上皮细胞和许多其他细胞类型能够检测感染或组织损伤,从而产生受调节的免疫反应。炎症小体是先天免疫的高度复杂和有效的协调者。这些寡聚多蛋白复合物处于各种先天免疫途径的中心,包括细胞骨架的调节、细胞因子的产生和成熟,以及细菌生长和细胞死亡的控制。炎性体组装通常导致 caspase-1 激活,这是一种炎性 caspase,参与细胞焦亡和炎性细胞因子的释放,以响应病原体模式和内源性危险刺激。然而,刺激和炎性体成分的性质是多种多样的。Caspase-1 激活介导成熟 IL-1β 和 IL-18 的释放,以响应由 NOD 样受体 (NLR) 和含有半胱天冬酶募集结构域 (ASC) 的凋亡相关斑点样蛋白引发的典型刺激。另一方面,caspase-11 描绘了一种非典型炎症小体,可促进细胞焦亡和非典型刺激的非焦亡功能。小鼠体内的 Caspase-11 及其在人体内的同源物 (caspase-4/5) 属于半胱氨酸蛋白酶 caspase-1 家族,在炎症中发挥作用。基因敲除小鼠为研究炎症性半胱天冬酶提供了新的遗传工具,并揭示了半胱天冬酶-11 在介导脓毒性休克中的作用,以应对致死剂量的脂多糖 (LPS)。LPS 的识别介导 caspase-11 的激活,它促进了无数的下游效应,包括焦亡和非焦亡效应功能。因此,caspase-11 的生理功能比之前确定的在细胞凋亡和细胞因子成熟中的作用要广泛得多。由外源性或内源性物质引起的炎症可能是有害的,如果过度,可能导致器官和组织损伤。因此,严格调节炎症小体通路的特异性和敏感性的复杂机制的存在提供了足够的免疫反应和最小的组织损伤之间的微调平衡。在这篇综述中,我们总结了 caspase-11 的效应功能。由外源性或内源性物质引起的炎症可能是有害的,如果过度,可能导致器官和组织损伤。因此,严格调节炎症小体通路的特异性和敏感性的复杂机制的存在提供了足够的免疫反应和最小的组织损伤之间的微调平衡。在这篇综述中,我们总结了 caspase-11 的效应功能。由外源性或内源性物质引起的炎症可能是有害的,如果过度,可能导致器官和组织损伤。因此,严格调节炎症小体通路的特异性和敏感性的复杂机制的存在提供了足够的免疫反应和最小的组织损伤之间的微调平衡。在这篇综述中,我们总结了 caspase-11 的效应功能。
更新日期:2020-08-28
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