The role of PERK and HRI mediated integrated stress response in Behçet's disease

Behçet's Disease (BD) is a systemic inflammatory disease characterized by recurrent oral and genital ulcers, uveitis and skin lesions. The etiology of BD is still unknown and it appears to be a more complex disease. The integrated stress response (ISR) pathway controls cellular responses to various stimuli. There are four kinases in the ISR pathway: PKR, GCN2, PERK and HRI. The main mechanism in ISR is phosphorylation of eIF2α by one or more of the four members of the ISR kinase family; this leads to a decrease in global protein synthesis, while upregulating the expression of a group of selected genes including ATF4. The purpose of the thesis study was to investigate the changes in gene expressions of eIF2α, PERK, HRI, HSPB8 and ATF4 in the ISR pathway in BD. Patient samples were obtained from 83 BD patients diagnosed in Istanbul University, Istanbul Faculty of Medicine, Department of Internal Diseases, Division of Rheumatology and 33 healthy control groups. In the study, expressions of target genes by qRT-PCR were analyzed in RNA material isolated from blood and synovial fluid samples. Our results showed that all targeted gene expression is altered in BD patients. In line with our findings, the ISR pathway has an important role in the pathogenesis of BD; however, we think that it can be targeted as new approaches in the diagnosis and treatment of the disease. We believe that further studies are needed to elucidate the role of the ISR pathway in the pathogenesis of BD. Key Words: Behçet's Disease, ISR, PERK, HRI, ATF4 The present work was supported by the Research Fund of Istanbul University. Project No. 36168