AlteredExpressionofUnfoldedProteinResponseGenesinMacrophagesfrom Behcet’s Disease

Endoplasmic reticulum (ER) stress triggers the unfolded protein response (UPR), which has been correlated with enhancedproduction of inflammatory cytokines. Given the important pathogenic roles of macrophages and inflammatory responses in theetiopathogenesis of Behcet’s disease (BD), this study aimed to assess the mRNA expression pattern of genes involved in theUPR pathway in macrophages from smoker and non-smoker BD patients. This case-control study was conducted between 2015and 2016 in Shariati Hospital, Tehran, Iran. Monocytes were enriched from obtained whole blood samples of 10 smokers and 10non-smoker BD patients as well as 10 healthy individuals. Using macrophage-colony stimulating factor (M-CSF), separatedmonocytes were differentiated into macrophages. After total RNA purification and cDNA synthesis, quantification analysis ofUPR genes, including activating transcription factor (ATF) 4, ATF6, X-box binding protein 1 (XBP1), binding immunoglobulinprotein (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 SYBRgreen master mix and real-time PCR. Among the measured genes, HERP mRNA was overexpressed in macrophages from BDpatients in comparison with healthy macrophages. HERP and GADD34 genes were upregulated in smoker BD patients comparedwith non-smoker BD patients as well as healthy subjects. Cigarette smoke can induce UPR gene expression in BD patients. Thealtered UPR gene expression in BD macrophages may contribute to BD pathogenesis.

Keywords:

Behcet’s syndrome , Macrophages , unfolded protein response