Altered Expression of Unfolded Protein Response Genes in Macrophages from Behcet’s Disease

Endoplasmic reticulum (ER) stress triggers the unfolded protein response (UPR), which has been correlated with enhanced production of inflammatory cytokines. Given the important pathogenic roles of macrophages and inflammatory responses in the etiopathogenesis of Behcet’s disease (BD), this study aimed to assess the mRNA expression pattern of genes involved in the UPR pathway in macrophages from smoker and non-smoker BD patients. This case-control study was conducted between 2015 and 2016 in Shariati Hospital, Tehran, Iran. Monocytes were enriched from obtained whole blood samples of 10 smoker and 10 non-smoker BD patients as well as 10 healthy individuals. Using macrophage-colony stimulating factor (M-CSF), separated monocytes were differentiated into macrophages. After total RNA purification and cDNA synthesis, quantification analysis of UPR genes, including activating transcription factor (ATF) 4, ATF6, X-box binding protein 1 (XBP1), binding immunoglobulin protein (BIP), C/EBP homologous protein (CHOP), homocysteine-inducible, endoplasmic reticulum stress-inducible, ubiquitin-like domain member 1 (HERP), and growth arrest and DNA damage-inducible protein (GADD34), was performed using SYBR green master mix and real-time PCR. Among the measured genes, HERP mRNA was overexpressed in macrophages from BD patients in comparison with healthy macrophages. HERP and GADD34 genes were upregulated in smoker BD patients compared with non-smoker BD patients as well as healthy subjects. Cigarette smoke can induce UPR gene expression in BD patients. The altered UPR gene expression in BD macrophages may contribute to BD pathogenesis.