McIntire Christian R, Yeretssian Garabet, Saleh Maya
Department of Biochemistry, McGill University, Montreal, QC, Canada.
Apoptosis. 2009 Apr;14(4):522-35. doi: 10.1007/s10495-009-0312-3.
Two of the main challenges that multicellular organisms faced during evolution were to cope with invading microorganisms and eliminate and replace dying cells. Our innate immune system evolved to handle both tasks. Key aspects of innate immunity are the detection of invaders or tissue injury and the activation of inflammation that alarms the system through the action of cytokine and chemokine cascades. While inflammation is essential for host resistance to infections, it is detrimental when produced chronically or in excess and is linked to various diseases, most notably auto-immune diseases, auto-inflammatory disorders, cancer and septic shock. Essential regulators of inflammation are enzymes termed "the inflammatory caspases". They are activated by cellular sensors of danger signals, the inflammasomes, and subsequently convert pro-inflammatory cytokines into their mature active forms. In addition, they regulate non-conventional protein secretion of alarmins and cytokines, glycolysis and lipid biogenesis, and the execution of an inflammatory form of cell death termed "pyroptosis". By acting as key regulators of inflammation, energy metabolism and cell death, inflammatory caspases and inflammasomes exert profound influences on innate immunity and infectious and non-infectious inflammatory diseases.
多细胞生物在进化过程中面临的两个主要挑战是应对入侵的微生物以及清除和替代死亡细胞。我们的先天免疫系统就是为应对这两项任务而进化的。先天免疫的关键方面包括对入侵者或组织损伤的检测以及炎症的激活,炎症通过细胞因子和趋化因子级联反应来警示系统。虽然炎症对于宿主抵抗感染至关重要,但长期或过度产生时则是有害的,并且与各种疾病相关,最显著的是自身免疫性疾病、自身炎症性疾病、癌症和脓毒性休克。炎症的关键调节因子是被称为“炎症性半胱天冬酶”的酶。它们由危险信号的细胞传感器——炎性小体激活,随后将促炎细胞因子转化为其成熟的活性形式。此外,它们调节警报素和细胞因子的非常规蛋白质分泌、糖酵解和脂质生物合成,以及一种被称为“细胞焦亡”的炎症形式的细胞死亡的执行。通过作为炎症、能量代谢和细胞死亡的关键调节因子,炎症性半胱天冬酶和炎性小体对先天免疫以及感染性和非感染性炎症性疾病产生深远影响。