Martins João D, Liberal Joana, Silva Ana, Ferreira Isabel, Neves Bruno Miguel, Cruz Maria Teresa
1 Center for Neuroscience and Cell Biology, University of Coimbra , Coimbra, Portugal .
DNA Cell Biol. 2015 Apr;34(4):274-81. doi: 10.1089/dna.2014.2752. Epub 2015 Mar 10.
Inflammation is a defensive response of the organism to manage harmful stimuli sensed by innate immune cells. The signal alarm is triggered by the recognition of pathogen-associated molecular patterns, such as microbial components, or host-derived damage-associated molecular patterns (DAMPs), namely high-mobility group box 1 protein (HMGB1) and purine metabolites, through a set of highly conserved receptors in immune cells termed pattern recognition receptors. Among these receptors, membrane-associated toll-like receptors (TLRs) and cytosolic nucleotide binding and oligomerization domain (nod)-like receptors (NLRs) assume particular relevance in the inflammatory process. Once activated, NLRs induce the assembly of multiprotein complexes called inflammasomes, leading to production of proinflammatory cytokines (e.g., interleukin-1) and induction of inflammatory cell death (pyroptosis) through the activation of caspase-1. Although these processes intend to protect the body from insults, prolonged or exacerbated inflammatory responses associated with inflammasome activation are related to a growing number of diseases. Recently, inflammasome activation and autophagy were shown to be linked and to mutually influence each other. Therefore, we aim, in this review, to discuss the recent evidences concerning the cross talk between autophagy and inflammasome activation and its potential roles in disease progression.
炎症是机体对先天免疫细胞感知到的有害刺激的一种防御反应。通过免疫细胞中一组高度保守的称为模式识别受体的受体，识别病原体相关分子模式（如微生物成分）或宿主来源的损伤相关分子模式（DAMPs），即高迁移率族蛋白盒1（HMGB1）和嘌呤代谢产物，触发信号警报。在这些受体中，膜相关的Toll样受体（TLRs）和胞质核苷酸结合寡聚化结构域（nod）样受体（NLRs）在炎症过程中具有特殊的相关性。一旦被激活，NLRs会诱导称为炎性小体的多蛋白复合物的组装，导致促炎细胞因子（如白细胞介素-1）的产生，并通过半胱天冬酶-1的激活诱导炎性细胞死亡（焦亡）。尽管这些过程旨在保护身体免受损伤，但与炎性小体激活相关的炎症反应延长或加剧与越来越多的疾病有关。最近，炎性小体激活和自噬被证明是相互关联且相互影响的。因此，在本综述中，我们旨在讨论自噬与炎性小体激活之间相互作用的最新证据及其在疾病进展中的潜在作用。
