Roles of the integrated stress response in regulation of inflammatory reactions

The integrated stress response (ISR) is a conserved cyto-protective mechanism, which has fundamental roles in maintaining cell viability under various conditions when intracellular and/or extracellular homeostasis is disrupted. ISR features phosphorylation of the alpha subunit of eukaryotic translation initiation factor 2 (eIF2α), leading to a global reduction in protein synthesis. Emerging evidence suggests that activation of ISR may have anti-inflammatory effects. In this concise review, we summarize the current experimental evidence in this regard from both in vitro and in vivo studies. It is suggested that ISR may represent a potential drug target for developing novel anti-inflammatory therapies.