Laboratory of Mucosal Exposome and Biomodulation, Department of Microbiology and Immunology, Pusan National University School of Medicine, Yangsan, South Korea.
Immunopharmacol Immunotoxicol. 2013 Apr;35(2):205-14. doi: 10.3109/08923973.2012.742535. Epub 2012 Dec 14.
Various cells are associated with the integrated stress response (ISR) that leads to translation arrest via phosphorylation of the alpha subunit of eukaryotic translation initiation factor 2. Pathogenic insults or nutritional imbalance in the mucosal tissues including the intestinal, airway, and genitourinary epithelia can cause ISRs, which have been linked to different mucosal inflammatory responses and subsequent systemic diseases. In particular, translational arrest caused by the early recognition of luminal microbes as well as nutritional status allows the human body to mount appropriate responses and maintain homeostasis both at the cellular and systemic levels. However, an over- or reduced ISR can create pathogenic conditions such as inflammation and carcinogenesis. This present review explores the association between eIF2α kinase-linked pathways and mucosal or systemic pro-inflammatory signals activated by xenobiotic insults (such as ones caused by microbes or nutritional abnormalities). Understanding ISR-modulated cellular alterations will provide progressive insights into approaches for treating human mucosal inflammatory and metabolic disorders.
各种细胞都与整合应激反应（ISR）有关，该反应通过磷酸化真核翻译起始因子 2 的α亚基导致翻译暂停。包括肠道、气道和泌尿生殖道上皮在内的黏膜组织中的病原体侵袭或营养失衡会导致 ISR，这与不同的黏膜炎症反应和随后的全身性疾病有关。特别是，由于早期识别腔微生物以及营养状况而导致的翻译暂停，使人体能够在细胞和全身水平上产生适当的反应并维持体内平衡。然而，过度或减少的 ISR 会导致炎症和癌变等致病条件。本综述探讨了 eIF2α 激酶相关途径与黏膜或全身促炎信号之间的关联，这些信号由外源性物质（如微生物或营养异常引起的物质）激活。了解 ISR 调节的细胞变化将为治疗人类黏膜炎症和代谢紊乱的方法提供新的思路。
