Immunity, Infection and Inflammation Program, Mater Medical Research Institute, Mater Hospitals, South Brisbane, Queensland, Australia.
Immunol Cell Biol. 2012 Mar;90(3):260-70. doi: 10.1038/icb.2011.112. Epub 2012 Jan 17.
Endoplasmic reticulum (ER) stress may be both a trigger and consequence of chronic inflammation. Chronic inflammation is often associated with diseases that arise because of primary misfolding mutations and ER stress. Similarly, ER stress and activation of the unfolded protein response (UPR) is a feature of many chronic inflammatory and autoimmune diseases. In this review, we describe how protein misfolding and the UPR trigger inflammation, how environmental ER stressors affect antigen presenting cells and immune effector cells, and present evidence that inflammatory factors exacerbate protein misfolding and ER stress. Examples from both animal models of disease and human diseases are used to illustrate the complex interactions between ER stress and inflammation, and opportunities for therapeutic targeting are discussed. Finally, recommendations are made for future research with respect to the interaction of ER stress and inflammation.
内质网(ER)应激可能既是慢性炎症的触发因素,也是其后果。慢性炎症通常与因主要错误折叠突变和 ER 应激而引起的疾病有关。同样,内质网应激和未折叠蛋白反应(UPR)的激活是许多慢性炎症性和自身免疫性疾病的特征。在这篇综述中,我们描述了蛋白质错误折叠和 UPR 如何引发炎症,环境 ER 应激源如何影响抗原呈递细胞和免疫效应细胞,并提供了炎症因子加剧蛋白质错误折叠和 ER 应激的证据。本文使用了来自疾病动物模型和人类疾病的例子来说明 ER 应激和炎症之间的复杂相互作用,并讨论了治疗靶向的机会。最后,就 ER 应激和炎症的相互作用提出了未来研究的建议。