Department of Physiological Chemistry, Genentech, Inc., South San Francisco, California 94080, USA.
Cold Spring Harb Perspect Biol. 2012 Mar 1;4(3):a006049. doi: 10.1101/cshperspect.a006049.
Inflammation is triggered when innate immune cells detect infection or tissue injury. Surveillance mechanisms involve pattern recognition receptors (PRRs) on the cell surface and in the cytoplasm. Most PRRs respond to pathogen-associated molecular patterns (PAMPs) or host-derived damage-associated molecular patterns (DAMPs) by triggering activation of NF-κB, AP1, CREB, c/EBP, and IRF transcription factors. Induction of genes encoding enzymes, chemokines, cytokines, adhesion molecules, and regulators of the extracellular matrix promotes the recruitment and activation of leukocytes, which are critical for eliminating foreign particles and host debris. A subset of PRRs activates the protease caspase-1, which causes maturation of the cytokines IL1β and IL18. Cell adhesion molecules and chemokines facilitate leukocyte extravasation from the circulation to the affected site, the chemokines stimulating G-protein-coupled receptors (GPCRs). Binding initiates signals that regulate leukocyte motility and effector functions. Other triggers of inflammation include allergens, which form antibody complexes that stimulate Fc receptors on mast cells. Although the role of inflammation is to resolve infection and injury, increasing evidence indicates that chronic inflammation is a risk factor for cancer.
当先天免疫细胞检测到感染或组织损伤时，就会引发炎症。监视机制涉及细胞表面和细胞质中的模式识别受体 (PRR)。大多数 PRR 通过触发 NF-κB、AP1、CREB、c/EBP 和 IRF 转录因子的激活来响应病原体相关分子模式 (PAMP) 或宿主来源的损伤相关分子模式 (DAMP)。诱导编码酶、趋化因子、细胞因子、粘附分子和细胞外基质调节剂的基因的表达促进白细胞的募集和激活，这对于消除外来颗粒和宿主碎片至关重要。PRR 的一部分激活蛋白酶半胱天冬酶-1，导致细胞因子 IL1β 和 IL18 的成熟。细胞粘附分子和趋化因子促进白细胞从循环到受影响部位的血管外渗，趋化因子刺激 G 蛋白偶联受体 (GPCR)。结合启动调节白细胞迁移和效应功能的信号。炎症的其他触发因素包括过敏原，过敏原形成刺激肥大细胞上的 Fc 受体的抗体复合物。尽管炎症的作用是解决感染和损伤，但越来越多的证据表明慢性炎症是癌症的一个风险因素。
