The Increased RNase Activity of IRE1α in PBMCs from Patients withRheumatoid Arthritis

摘要

Purpose: Despite recent advances in the diagnosis and treatment of rheumatoid arthritis (RA), thisinflammatory disease remains a challenge to patients and physicians. Recent evidence highlightsthe contribution of endoplasmic reticulum (ER) stress in the pathogenesis and treatment of RA.Herein, we study the expression of the ER stress sensor inositol-requiring enzyme 1α (IRE1α),as well as XBP1 splicing and the regulated IRE1-dependent decay (RIDD), in peripheral bloodmononuclear cells (PBMCs) from patients with RA compared with healthy controls.Methods: The PBMCs from blood samples of RA patients and healthy volunteers were isolatedby a density gradient centrifugation method using Ficoll. The gene expression levels of GRP78/Bip, IRE1, XBP1s, micro-RNAs (miRNAs) were evaluated by real-time PCR.Results: The expression of GRP78, IRE1, and XBP1s were increased in PBMCs of RA patientscompared with healthy controls. We further show that the RIDD targets (miRNA-17, -34a, -96,and -125b) were downregulated in RA samples.Conclusion: This study can expand our knowledge on the importance of RNase activity ofIRE1α in RA and may offer new potentials for developing novel diagnostic and/or therapeuticbiomarkers.